Khan A

References (45)

Title : Synthesis, biochemical and computational evaluations of novel bis-acylhydrazones of 2,2'-(1,1'-biphenyl)-4,4'-diylbis(oxy))di(acetohydrazide) as dual cholinesterase inhibitors - Ibrahim_2024_Bioorg.Chem_144_107144
Author(s) : Ibrahim M , Halim SA , Latif A , Ahmad M , Ali S , Ullah S , Khalid A , Abdalla AN , Khan A , Al-Harrasi A , Ali M
Ref : Bioorg Chem , 144 :107144 , 2024
Abstract : A series of twenty-seven bis(acylhydrazones) were successfully synthesized with high yields through a multistep process, which entailed the esterification of hydroxyl groups, hydrazination with an excess of hydrazine hydrate, and subsequent reactions with various carbonyl moieties (aldehydes). In the final stage of synthesis, different chemical species including aromatic, heterocyclic, and aliphatic compounds were integrated into the framework. The resulting compounds were characterized using several spectroscopic techniques ((1)H NMR, (13)C NMR, and mass spectrometry). Their anticholinesterase activities were assessed in vitro by examining their interactions with two cholinesterase enzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the synthesized hits, compounds 3, 5, 6, 9-12, and 14 exhibited good to moderate inhibition of AChE. Specifically, 10 (IC(50) = 26.3 +/- 0.4 microM) and 11 (IC(50) = 28.4 +/- 0.5 microM) showed good inhibitory activity against AChE, while 9, 12, 3, and 6 exhibited significant inhibition potential against AChE with IC(50) values ranging from 35.2 +/- 1.1 microM to 64.4 +/- 0.3 microM. On the other hand, 5 (IC(50) = 22.0 +/- 1.1 microM) and 27 (IC(50) = 31.3 +/- 1.3 microM) displayed significant, and 19 (IC(50) = 92.6 +/- 0.4 microM) showed moderate inhibitory potential for BChE. Notably, 5 and 27 exhibited dual inhibition of AChE and BChE, with greater potency than the standard drug galantamine. The binding patterns of these molecules within the binding cavities of AChE and BChE were anticipated by molecular docking which showed good correlation with our in vitro findings. Further structural optimization of these molecules may yield more potent AChE and BChE inhibitors.
ESTHER : Ibrahim_2024_Bioorg.Chem_144_107144
PubMedSearch : Ibrahim_2024_Bioorg.Chem_144_107144
PubMedID: 38281382

Title : Discovery of Quinolinone Hybrids as Dual Inhibitors of Acetylcholinesterase and Abeta Aggregation for Alzheimer's Disease Therapy - Manzoor_2023_ACS.Chem.Neurosci__
Author(s) : Manzoor S , Gabr MT , Nafie MS , Raza MK , Khan A , Nayeem SM , Arafa RK , Hoda N
Ref : ACS Chem Neurosci , : , 2023
Abstract : The development of multitargeted therapeutics has evolved as a promising strategy to identify efficient therapeutics for neurological disorders. We report herein new quinolinone hybrids as dual inhibitors of acetylcholinesterase (AChE) and Abeta aggregation that function as multitargeted ligands for Alzheimer's disease. The quinoline hybrids (AM1-AM16) were screened for their ability to inhibit AChE, BACE1, amyloid fibrillation, alpha-syn aggregation, and tau aggregation. Among the tested compounds, AM5 and AM10 inhibited AChE activity by more than 80% at single-dose screening and possessed a remarkable ability to inhibit the fibrillation of Abeta(42) oligomers at 10 microM. In addition, dose-dependent screening of AM5 and AM10 was performed, giving half-maximal AChE inhibitory concentration (IC(50)) values of 1.29 +/- 0.13 and 1.72 +/- 0.18 microM, respectively. In addition, AM5 and AM10 demonstrated concentration-dependent inhibitory profiles for the aggregation of Abeta(42) oligomers with estimated IC(50) values of 4.93 +/- 0.8 and 1.42 +/- 0.3 microM, respectively. Moreover, the neuroprotective properties of the lead compounds AM5 and AM10 were determined in SH-SY5Y cells incubated with Abeta oligomers. This work would enable future research efforts aiming at the structural optimization of AM5 and AM10 to develop potent dual inhibitors of AChE and amyloid aggregation. Furthermore, the in vivo assay confirmed the antioxidant activity of compounds AM5 and AM10 through increasing GSH, CAT, and SOD activities that are responsible for scavenging the ROS and restoring its normal level. Blood investigation illustrated the protective activity of the two compounds against lead-induced neurotoxicity through retaining hematological and liver enzymes near normal levels. Finally, immunohistochemistry investigation revealed the inhibitory activity of beta-amyloid (Abeta) aggregation.
ESTHER : Manzoor_2023_ACS.Chem.Neurosci__
PubMedSearch : Manzoor_2023_ACS.Chem.Neurosci__
PubMedID: 38149821

Title : Genome wide identification of GDSL gene family explores a novel GhirGDSL26 gene enhancing drought stress tolerance in cotton - Liu_2023_BMC.Plant.Biol_23_14
Author(s) : Liu J , Wang H , Khan A , Xu Y , Hou Y , Wang Y , Zhou Z , Zheng J , Liu F , Cai X
Ref : BMC Plant Biol , 23 :14 , 2023
Abstract : BACKGROUND: Current climate change scenarios are posing greater threats to the growth and development of plants. Thus, significant efforts are required that can mitigate the negative effects of drought on the cotton plant. GDSL esterase/lipases can offer an imperative role in plant development and stress tolerance. However, thesystematic and functional roles of the GDSL gene family, particularly in cotton under water deficit conditions have not yet been explored. RESULTS: In this study, 103, 103, 99, 198, 203, 239, 249, and 215 GDSL proteins were identified in eight cotton genomes i.e., Gossypium herbaceum (A1), Gossypium arboretum (A2), Gossypium raimondii (D5), Gossypium hirsutum (AD1), Gossypium barbadense (AD2), Gossypium tomentosum (AD3), Gossypium mustelinum (AD4), Gossypium darwinii (AD5), respectively. A total of 198 GDSL genes of Gossypium hirsutum were divided into eleven clades using phylogenetic analysis, and the number of GhirGDSL varied among different clades. The cis-elements analysis showed that GhirGDSL gene expression was mainly related to light, plant hormones, and variable tense environments. Combining the results of transcriptome and RT-qPCR, GhirGDSL26 (Gh_A01G1774), a highly up-regulated gene, was selected for further elucidating its tole in drought stress tolerance via estimating physiological and biochemical parameters. Heterologous expression of the GhirGDSL26 gene in Arabidopsis thaliana resulted in a higher germination and survival rates, longer root lengths, lower ion leakage and induced stress-responsive genes expression under drought stress. This further highlighted that overexpressed plants had a better drought tolerance as compared to the wildtype plants. Moreover, 3, 3'-diaminobenzidine (DAB) and Trypan staining results indicated reduced oxidative damage, less cell membrane damage, and lower ion leakage in overexpressed plants as compared to wild type. Silencing of GhirGDSL26 in cotton via VIGS resulting in a susceptible phenotype, higher MDA and H(2)O(2) contents, lower SOD activity, and proline content. CONCLUSION: Our results demonstrated that GhirGDSL26 plays a critical role in cotton drought stress tolerance. Current findings enrich our knowledge of GDSL genes in cotton and provide theoretical guidance and excellent gene resources for improving drought tolerance in cotton.
ESTHER : Liu_2023_BMC.Plant.Biol_23_14
PubMedSearch : Liu_2023_BMC.Plant.Biol_23_14
PubMedID: 36609252

Title : Natural coumarins from Murraya paniculata as mixed-type inhibitors of cholinesterases: In vitro and in silico investigations - Khalid_2023_Front.Pharmacol_14_1133809
Author(s) : Khalid A , Khan W , Zia K , Azizuddin , Ahsan W , Alhazmi HA , Abdalla AN , Najmi A , Khan A , Bouyahya A , Ul-Haq Z
Ref : Front Pharmacol , 14 :1133809 , 2023
Abstract : Currently, acetylcholinesterase (AChE) inhibiting drugs in clinical use, such as tacrine, donepezil, rivastigmine, and galanthamine, are associated with serious side effects and short half-lives. In recent years, numerous phytochemicals have been identified as inhibitors of cholinesterases with potential applications in the management of Alzheimer's disease (AD). In this study three natural coumarins, 2'-O-ethylmurrangatin (1), murranganone (2), and paniculatin (3) isolated previously by our group from the leaves of Murraya paniculata, were tested against the two cholinesterases (ChE) enzymes, AChE and butyrylcholinesterase (BChE) using in vitro assay. Molecular docking was performed to highlight the structural properties that contribute to the molecular recognition pattern in the inhibition of ChE and the structural differences resulting in the selectivity of these compounds toward AChE. Classical enzyme inhibition kinetics data suggested that compounds 2 and 3 were potent inhibitors of AChE and BChE, while 1 was found inactive against both enzymes. The findings from molecular docking studies revealed the competitive and non-competitive inhibition mechanisms of compounds 2 and 3 against both enzymes. Molecular docking and simulations have revealed that hydrogen bonding, mediated by ketone and hydroxyl functionalities in various positions, significantly contributes to the binding of the inhibitor to the receptor. According to MD simulation studies, the stability of the ligand-AChE complex for the most active compound (3) is found to be comparable to that of the widely used drug Tacrine. In addition, to evaluate the drug-likeness of compounds, in silico ADME evaluation was performed, and the compounds presented good ADME profiles. Data suggested that the coumarin nucleus having diverse side chains at the C-8 position can serve as a potential inhibitor of cholinesterases and can act as a lead to develop a new semisynthetic drug for the treatment of AD.
ESTHER : Khalid_2023_Front.Pharmacol_14_1133809
PubMedSearch : Khalid_2023_Front.Pharmacol_14_1133809
PubMedID: 36969847

Title : Antiamnesic Effects of Novel Phthalimide Derivatives in Scopolamine-Induced Memory Impairment in Mice: A Useful Therapy for Alzheimer's Disease - Karim_2023_ACS.Omega_8_8052
Author(s) : Karim N , Khan I , Halim SA , Khalid A , Abdalla AN , Rehman NU , Khan A , Al-Harrasi A
Ref : ACS Omega , 8 :8052 , 2023
Abstract : Phthalimides have diverse bioactivities and are attractive molecules for drug discovery and development. Here, we explored new synthesized phthalimide derivatives (compounds 1-3) in improving memory impairment associated with Alzheimer's disease (AD), using in vitro and ex vivo acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition and in vivo models, including Y-maze test and novel object recognition test (NORT). Compounds 1-3 exhibited significant AChE activity with IC(50) values of 10, 140, and 18 microM and BuChE with IC(50) values of 80, 50, and 11 microM, respectively. All compounds 1-3 showed excellent antioxidant potential in DPPH and ABTS assays with IC(50) values in the range of 105-340 and 205-350 microM, respectively. In ex vivo studies, compounds 1-3 also significantly inhibited both enzymes in a concentration-dependent manner along with significant antioxidant activities. In in vivo studies, compounds 1-3 reversed scopolamine-induced amnesia as indicated by a significant increase in the spontaneous alternation in the Y-maze test and an increase in the discrimination index in the NORT. Molecular docking was also conducted for compounds 1-3 against AChE and BuChE, which showed that compounds 1 and 3 have excellent binding with AChE and BuChE as compared to 2. These findings suggest that compounds 1-3 possess significant antiamnesic potential and may serve as useful leads to develop novel therapeutics for the symptomatic management and treatment of AD.
ESTHER : Karim_2023_ACS.Omega_8_8052
PubMedSearch : Karim_2023_ACS.Omega_8_8052
PubMedID: 36872974

Title : Substrate-like novel inhibitors of prolyl specific oligo peptidase for neurodegenerative disorders - Khan_2023_J.Biomol.Struct.Dyn__1
Author(s) : Khan M , Halim SA , Waqas M , Golmohammadi F , Balalaie S , Csuk R , Uddin J , Khan A , Al-Harrasi A
Ref : J Biomol Struct Dyn , :1 , 2023
Abstract : Prolyl specific oligopeptidase (POP), is one of the highly expressed enzymes in the brain and is a prime target to treat disorders related to the central nervous system. Here, we describe the structure-based design of the tacrine derivatives, selective, and brain-permeable POP inhibitors. These compounds inactivate POP in-vitro specifically and sustainably at very low concentrations (nano molar). Among this series, compound 6b (IC(50) = 0.81 +/- 0.04 microM) exhibited most potent inhibition. Furthermore, kinetic study revealed that these molecules target active site of POP which is further confirmed by in-silico molecular interaction analysis. The computational docking results indicates that the compounds are well fitted in the active site with high binding score (i.e., > -7 to > -4 kcal/mol) where Trp595, Arg643, Tyr473, and Ser554 plays important role in binding with the active compounds. The molecular dynamic simulation of most active compounds (6a, 6b, 6d, and 6f) displayed higher free energy binding, when compared to the standard drug in MM-PBSA based binding free energy calculation. In addition, the predicted pharmacokinetic profile suggests that these compounds can serve as excellent inhibitors upon additional optimization which makes them prime choice for further investigation.Communicated by Ramaswamy H. Sarma.
ESTHER : Khan_2023_J.Biomol.Struct.Dyn__1
PubMedSearch : Khan_2023_J.Biomol.Struct.Dyn__1
PubMedID: 37608559
Gene_locus related to this paper: pig-ppce

Title : Inhibition of Acetylcholinesterase with Novel 1, 3, 4, Oxadiazole Derivatives: A Kinetic, In Silico, and In Vitro Approach - Begum_2023_ACS.Omega_8_46816
Author(s) : Begum F , Yousaf M , Iqbal S , Ullah N , Hussain A , Khan M , Khalid A , Algarni AS , Abdalla AN , Khan A , Lodhi MA , Al-Harrasi A
Ref : ACS Omega , 8 :46816 , 2023
Abstract : Alzheimer's disease (AD) is a neurological disease that disturbs the memory, thinking skills, and behavior of the affected person. AD is a complex disease caused by the breakdown of acetylcholine via acetylcholinesterase (AChE). The present study aimed to assess the synthetic inhibitors of AChE that could be used to treat AD. For this purpose, synthetic compounds of oxadiazole derivatives (15-35) were evaluated and identified as promising inhibitors of AChE, exhibiting IC(50) varying between 41.87 +/- 0.67 and 1580.25 +/- 0.7 microM. The kinetic parameters indicated that all the studied compounds bind to the allosteric site and decrease the efficiency of the AChE enzyme. In silico docking analysis showed that the majority of the compounds interact with the anionic subsite and Per-Arnt-Sim domain of AChE and are stabilized by various bonds including Pi-Pi and hydrogen bonding. The stability of the most potent compounds 16 and 17 with AChE interaction was confirmed by molecular dynamics simulations. Moreover, all compounds exhibited concentration-dependent calcium (Ca(2+)) antagonistic and spasmolytic activities. Among the whole series of oxadiazole derivatives, compounds 16 and 17 displayed the highest activities on spontaneous and potassium (K(+))-induced contraction. Therefore, the AChE inhibitory potential, cytotoxicity safe profile, and Ca(2+) antagonistic ability of these compounds make them potential therapeutic agents against AD and its associated problems in the future.
ESTHER : Begum_2023_ACS.Omega_8_46816
PubMedSearch : Begum_2023_ACS.Omega_8_46816
PubMedID: 38107974

Title : Antioxidant, LC-MS Analysis, and Cholinesterase Inhibitory Potentials of Phoenix dactylifera Cultivar Khudari: An In Vitro Enzyme Kinetics and In Silico Study - Almalki_2023_Biomolecules_13_
Author(s) : Almalki SG , Alqurashi YE , Alturaiki W , Almawash S , Khan A , Ahmad P , Iqbal D
Ref : Biomolecules , 13 : , 2023
Abstract : We evaluated the therapeutic potentials of Khudari fruit pulp, a functional food and cultivar of Phoenix dactylifera, against neurological disorders. Our results demonstrate a good amount of phytochemicals (total phenolic content: 17.77 +/- 8.21 microg GA/mg extract) with a high antioxidant potential of aqueous extract (DPPH assay IC(50) = 235.84 +/- 11.65 microg/mL) and FRAP value: 331.81 +/- 4.56 micromol. Furthermore, the aqueous extract showed the marked inhibition of cell-free acetylcholinesterase (electric eel) with an IC(50) value of 48.25 +/- 2.04 microg/mL, and an enzyme inhibition kinetics study revealed that it exhibits mixed inhibition. Thereafter, we listed the 18 best-matched phytochemical compounds present in aqueous extract through LC/MS analysis. The computational study revealed that five out of eighteen predicted compounds can cross the BBB and exert considerable aqueous solubility. where 2-{5-[(1E)-3-methylbuta-1,3-dien-1-yl]-1H-indol-3-yl}ethanol (MDIE) indicates an acceptable LD(50). value. A molecular docking study exhibited that the compounds occupied the key residues of acetylcholinesterase with deltaG range between -6.91 and -9.49 kcal/mol, where MDIE has deltaG: -8.67 kcal/mol, which was better than that of tacrine, deltaG: -8.25 kcal/mol. Molecular dynamics analyses of 100 ns supported the stability of the protein-ligand complexes analyzed through RMSD, RMSF, Rg, and SASA parameters. TRP_84 and GLY_442 are the most critical hydrophobic contacts for the complex, although GLU_199 is important for H-bonds. Prime/MM-GBSA showed that the protein-ligand complex formed a stable confirmation. These findings suggest that the aqueous extract of Khudari fruit pulp has significant antioxidant and acetylcholinesterase inhibition potentials, and its compound, MDIE, forms stably with confirmation with the target protein, though this fruit of Khudari dates can be a better functional food for the treatment of Alzheimer's disease. Further investigations are needed to fully understand the therapeutic role of this plant-based compound via in vivo study.
ESTHER : Almalki_2023_Biomolecules_13_
PubMedSearch : Almalki_2023_Biomolecules_13_
PubMedID: 37892156

Title : Triacylglycerol lipase, OsSG34, plays an important role in grain shape and appearance quality in rice - Jin_2023_Plant.J__
Author(s) : Jin X , Chen J , Khan A , Chen Z , Gao R , Lu Y , Zheng X
Ref : Plant J , : , 2023
Abstract : Optimal grain-appearance quality is largely determined by grain size. To date, dozens of grain size-related genes have been identified. However, the regulatory mechanism of slender grain formation is not fully clear. We identified the OsSG34 gene by map-based cloning. A 9-bp deletion on 5'-untranslated region of OsSG34, which resulted in the expression difference between the wild-type and sg34 mutant, led to the slender grains and good transparency in sg34 mutant. OsSG34 as an alpha/beta fold triacylglycerol lipase affected the triglyceride content directly, and the components of cell wall indirectly, especially the lignin between the inner and outer lemmas in rice grains, which could affect the change in grain size by altering cell proliferation and expansion, while the change in starch content and starch granule arrangement in endosperm could affect the grain-appearance quality. Moreover, the OsERF71 was identified to directly bind to cis-element on the mutant site, thereby regulating the OsSG34 expression. Knockout of three OsSG34 homologous genes resulted in slender grains as well. The study demonstrated OsSG34, involved in lipid metabolism, affected grain size and quality. Our findings suggest that the OsSG34 gene could be used in rice breeding for high yield and good grain-appearance quality via marker-assisted selection and gene-editing approaches.
ESTHER : Jin_2023_Plant.J__
PubMedSearch : Jin_2023_Plant.J__
PubMedID: 37938788
Gene_locus related to this paper: orysa-Q8H025 , orysa-Q8H024 , orysa-Q8RUY8 , orysa-Q7XI46 , orysa-q75lp9

Title : An exploration of binding of Hesperidin, Rutin, and Thymoquinone to acetylcholinesterase enzyme using multi-level computational approaches - Mir_2023_J.Biomol.Struct.Dyn__1
Author(s) : Mir SA , Nayak B , Khan A , Khan MI , Eldakhakhny BM , Arif DO
Ref : J Biomol Struct Dyn , :1 , 2023
Abstract : Alzheimer's disease, an intricate neurological disorder, is impacting an ever-increasing number of individuals globally, particularly among the aging population. For several decades phytochemicals were used as Ayurveda to treat both communicable and non-communicable diseases. Acetylcholinesterase (AChE) is a widely chosen therapeutic target for the development of early prevention and effective management of neurodegenerative diseases. The primary objective of the present study was to investigate the binding potential between Rutin Thymoquinone, Hesperidin and the FDA-approved drug Donepezil with AChE. Additionally, a comparative analysis was conducted. These phytochemicals were docked with the binding site of the AChE experimental complex. The molecular dockings demonstrated that the Hesperidinh showed a better binding affinity of -22.0631 kcal/mol. The ADME/T investigations revealed that the selected phytochemicals are non-toxic and drug-like candidates. Molecular dynamics simulations were implemented to determine the conformational changes of Rutin, hesperidin, Thymoquinone, and Donepezil complexed with AChE. Hesperidin and Donepezil were more stable than Rutin, Thymoquinone complexed with AChE. Next, essential dynamics and defining the secondary structure of protein were to determine the conformational changes in AChE complexed with selected phytochemicals during simulations. Overall, the MD Simulations demonstrated that all complexes in this study achieved stability until 100 ns of the simulation period was performed thrice. The structural analysis of AChE was done using multiple search engines to explore the molecular functions, biological processes, and pathways in which AChE proteins are involved and to identify potential drug targets for various diseases. This present study concludes that Hesperidin was found to be a more potent AChE inhibitors than Rutin, and further experiments are required to determine the effectivity of Hesperidin against neurodegenerative diseases.Communicated by Ramaswamy H. Sarma.
ESTHER : Mir_2023_J.Biomol.Struct.Dyn__1
PubMedSearch : Mir_2023_J.Biomol.Struct.Dyn__1
PubMedID: 37811769

Title : New supramolecules of bis(acylhydrazones)-linked bisphenol sulfide for Alzheimer's: targeting cholinesterases by in vitro and in silico approaches - Ibrahim_2023_RSC.Adv_13_25379
Author(s) : Ibrahim M , Ali M , Halim SA , Latif A , Ahmad M , Ali S , SameeUllah , Khan A , Rebierio AI , Uddin J , Al-Harrasi A
Ref : RSC Adv , 13 :25379 , 2023
Abstract : In current research, two functional components, i.e., hydrazone and bisphenol sulfide were combined to get useful supramolecules in medicinal chemistry. Herein 25 new 4,4'-thiodiphenol bis-acylhydrazones were synthesized in good to excellent yields. Initially ethyl-2-chloroacetate was reacted with 4,4'-thiodiphenol, which was further reacted with excess hydrazine hydrate to produce 2,2'-((thiobis(4,1-phenylene))bis(oxy))di(acetohydrazide), which was then combined with various aromatic and aliphatic aldehydes to get the desired products (hydrazones, 4a-4y). The synthesized supramolecules were characterized by contemporary spectroscopic techniques such as (1)H NMR, (13)C NMR, and mass spectroscopy. The synthetic compound's cholinesterase blocking activity was tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes where compounds 4n, and 4h showed excellent inhibitory potential for AChE, while 4b, and 4h, demonstrated most potent inhibition of BChE. The starting compound (SM3) and compounds 4h and SM3 depicted excellent dual inhibitory capabilities for both enzymes. The chemical basis of anticholinesterase activity was investigated using a structure-based molecular docking approach. The biological significance and the ease of synthesis of this class of compounds should be considered in therapeutic development for Alzheimer's disease treatments.
ESTHER : Ibrahim_2023_RSC.Adv_13_25379
PubMedSearch : Ibrahim_2023_RSC.Adv_13_25379
PubMedID: 37636505

Title : Density Functional Theory Calculations and Molecular Docking Analyses of Flavonoids for Their Possible Application against the Acetylcholinesterase and Triose-Phosphate Isomerase Proteins of Rhipicephalus microplus - Malak_2023_Molecules_28_
Author(s) : Malak N , Alotaibi BS , Khan A , Ullah S , Nasreen N , Niaz S , Chen CC
Ref : Molecules , 28 : , 2023
Abstract : Ticks and tick-borne diseases constitute a substantial hazard to the livestock industry. The rising costs and lack of availability of synthetic chemical acaricides for farmers with limited resources, tick resistance to current acaricides, and residual issues in meat and milk consumed by humans further aggravate the situation. Developing innovative, eco-friendly tick management techniques, such as natural products and commodities, is vital. Similarly, searching for effective and feasible treatments for tick-borne diseases is essential. Flavonoids are a class of natural chemicals with multiple bioactivities, including the inhibition of enzymes. We selected eighty flavonoids having enzyme inhibitory, insecticide, and pesticide properties. Flavonoids' inhibitory effects on the acetylcholinesterase (AChE1) and triose-phosphate isomerase (TIM) proteins of Rhipicephalus microplus were examined utilizing a molecular docking approach. Our research demonstrated that flavonoids interact with the active areas of proteins. Seven flavonoids (methylenebisphloridzin, thearubigin, fortunellin, quercetagetin-7-O-(6-O-caffeoyl-beta-d-glucopyranoside), quercetagetin-7-O-(6-O-p-coumaroyl-beta-glucopyranoside), rutin, and kaempferol 3-neohesperidoside) were the most potent AChE1 inhibitors, while the other three flavonoids (quercetagetin-7-O-(6-O-caffeoyl-beta-d-glucopyranoside), isorhamnetin, and liquiritin) were the potent inhibitors of TIM. These computationally-driven discoveries are beneficial and can be utilized in assessing drug bioavailability in both in vitro and in vivo settings. This knowledge can create new strategies for managing ticks and tick-borne diseases.
ESTHER : Malak_2023_Molecules_28_
PubMedSearch : Malak_2023_Molecules_28_
PubMedID: 37110838

Title : Antiamnesic Effects of Feralolide Isolated from Aloe&\;amp\;nbsp\;vera Resin Miller against Learning Impairments Induced in Mice - Khan_2023_Antioxidants.(Basel)_12_
Author(s) : Khan I , Mohanta TK , Ihsan N , Halim SA , Khan A , Rehman NU , Khan F , Khalid A , Abdalla AN , Karim N , Al-Harrasi A
Ref : Antioxidants (Basel) , 12 : , 2023
Abstract : Feralolide, a dihydroisocoumarin, was isolated from the methanolic extract of resin of Aloe vera. The present study aims to investigate the in vivo ability of feralolide to ameliorate memory impairment induced by scopolamine using a battery of in vitro assays, such as antioxidant and acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition, and in vivo animal models, including elevated plus maze, Morris water maze, passive avoidance, and novel object recognition tests. Feralolide caused a concentration-dependent inhibition of AChE and BuChE enzymes with IC(50) values of 55 and 52 microg/mL, respectively, and antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) with IC(50) values 170 and 220 microg/mL, respectively. Feralolide reversed the scopolamine-induced amnesia as indicated by a dose-dependent decrease in escape latency, path length, and passing frequency in the Morris water maze test compared with the relevant control. The compound also significantly increased the discrimination index in a dose-dependent manner in NORT and decreased transfer latency in EPM, reflective of its memory-enhancing effect. Furthermore, feralolide also caused significant dose-dependent elevation in the step-down latency (SDL) in the passive avoidance test. The results indicated that feralolide might be a helpful memory restorative mediator in treating cognitive disorders such as Alzheimer's disease.
ESTHER : Khan_2023_Antioxidants.(Basel)_12_
PubMedSearch : Khan_2023_Antioxidants.(Basel)_12_
PubMedID: 36671023

Title : 2-Mercaptobenzimidazole clubbed hydrazone for Alzheimer's therapy: In vitro, kinetic, in silico, and in vivo potentials - Begum_2022_Front.Pharmacol_13_946134
Author(s) : Begum F , Rehman NU , Khan A , Iqbal S , Paracha RZ , Uddin J , Al-Harrasi A , Lodhi MA
Ref : Front Pharmacol , 13 :946134 , 2022
Abstract : Alzheimer's is a type of dementia that affects the affected person's thinking, memory, and behavior. It is a multifactorial disease, developed by the breakdown of the neurotransmitter acetylcholine via acetylcholinesterase (AChE). The present study was designed to evaluate potential inhibitors of acetylcholinesterase that could be used as a therapeutic agent against Alzheimer's disease (AD). For this course, synthetic compounds of the Schiff bases class of 2-mercaptobenzimidazole hydrazone derivatives (9-14) were determined to be potent acetylcholinesterase inhibitors with IC(50) values varying between 37.64 +/- 0.2 and 74.76 +/- 0.3 microM. The kinetic studies showed that these are non-competitive inhibitors of AChE. Molecular docking studies revealed that all compounds accommodate well in the active site and are stabilized by hydrophobic interactions and hydrogen bonding. Molecular dynamics (MD) simulations of selected potent inhibitors confirm their stability in the active site of the enzyme. Moreover, all compounds showed antispasmodic and Ca(2+) antagonistic activities. Among the selected compounds of 2-mercaptobenzimidazole hydrazone derivatives, compound 11 exhibited the highest activity on spontaneous and K(+)-induced contractions, followed by compound 13. Therefore, the Ca(2+) antagonistic, AChE inhibition potential, and safety profile of these compounds in the human neutrophil viability assay make them potential drug candidates against AD in the future.
ESTHER : Begum_2022_Front.Pharmacol_13_946134
PubMedSearch : Begum_2022_Front.Pharmacol_13_946134
PubMedID: 36059999

Title : In silico approaches to develop herbal acaricides against R. (Boophilus) Microplus and In vitro Anti-Tick activities of selected medicinal plants - Malak_2022_Saudi.J.Biol.Sci_29_103302
Author(s) : Malak N , Niaz S , Wadood A , Nasreen N , Ali I , Iqbal J , Swelum AA , Ezzat Ahmed A , Alkahtani MA , Zajac Z , Khan A
Ref : Saudi J Biol Sci , 29 :103302 , 2022
Abstract : In tropical and sub-tropical areas of the world the most damaging pest of the livestock sector are cattle tick, Rhipicephalus microplus. The current study was aimed to generate phytochemical derived acaricides to control Rhipicephalus microplus populations, to maintain livestock herd production, minimize economic losses and to reduce uses of man-made chemicals acaricides. To achieve this goal, Adult immersion and larval package test were used to determine the feasibility of Berberium lyceum and Tamarixa aphylla against Rhipicephalus microplus ticks. Further, an In silico technique was employed to discover biologically active substances from both plants using docking method. Berberium lyceum and Tamarixa aphylla exhibited a reasonably high fatal effect at 40.0 mg/L on egg laying (index of egg laying = 0.19 and 0.19) respectively, thus inhibiting the oviposition (49.5 and 45.1, respectively) and the larval mortality (97% and 93%, respectively). Further, we also used Chem-Draw ultra-software (v. 12.0.2.1076. 2010) to illustrate different structures of38 known bioactive phytochemicals which are discovered in the PubChem database and verify the hypothesis that tick inhibition was linked to acetylcholinesterase (AChE). Barbamunine and rutin from Berberium lyceum showed remarkable interaction with RmAChE1 active site residues with docking scores of -9.11 to -8.71 while phytol and dehydrodigallic acid from Tamarix aphylla showed comparable docking scores of -7.17 and -7.14 respectively against Rhipicephalus microplus acetylcholinesterase protein. Based on obtained result, we believe that Berberium lyceum and Tamarixa aphylla bioactive components could be potential candidates in the control and management of Rhipicephalus microplus and should be studied further as a supplement or replacement for synthetic acaricides.
ESTHER : Malak_2022_Saudi.J.Biol.Sci_29_103302
PubMedSearch : Malak_2022_Saudi.J.Biol.Sci_29_103302
PubMedID: 35602870

Title : Comparative in-vitro anti-inflammatory, anticholinesterase and antidiabetic evaluation: computational and kinetic assessment of succinimides cyano-acetate derivatives - Pervaiz_2022_J.Biomol.Struct.Dyn__1
Author(s) : Pervaiz A , Jan MS , Hassan Shah SM , Khan A , Zafar R , Ansari B , Shahid M , Hussain F , Ijaz Khan M , Zeb A , Mukarram Shah SM
Ref : J Biomol Struct Dyn , :1 , 2022
Abstract : This research was planned to synthesize cyano-acetate derivatives of succinimide and evaluate its comparative biological efficacy as anti-inflammatory, anti-cholinesterase and anti-diabetic, which was further validated by molecular docking studies. The three cyano-acetate derivatives of succinimide including compound 23 Methyl 2-cyano-2-(2,5-dioxopyrrolidin-3-yl)acetate, compound 31 Methyl 2-cyano-2-(1-methyl-2,5-dioxopyrrolidin-3-yl)acetate and compound 44 Methyl 2-cyano-2-(1-ethyl-2,5-dioxopyrrolidin-3-yl) acetate were synthesized. The mentioned compounds were checked for in vitro anti-inflammatory, anti-cholinesterase and anti-diabetic (alpha-amylase inhibition) activity. To validate the in vitro results, computational studies were carried out using molecular operating environment to analyse the BE, i.e. binding energies of all synthesized compounds against the respective enzymes. The Compounds 23, 31, 44 exhibited anti-inflammatory via inhibiting COX-2 (IC(50) value of 204.08, 68.60 and 50.93 microM, respectively), COX-1 (IC(50) value of 287, 185, and 143 microM, respectively) and 5-LOX (IC(50) value of 138, 50.76 and 20, 87 microM respectively)(.) They exhibited choline-mimetic potential, such as compound 23, 31 and 44 inhibited AChE enzyme (IC(50) value of 240, 174, and 134 microM, respectively) and BChE enzyme (IC(50) value of 203, 134 and 97 microM, respectively). The Compounds 23, 31, 44 exhibited anti-diabetic effect via inhibiting alpha-amylase enzyme (IC(50) values of 250, 106 and 60 microM, respectively). Molecular docking studies revealed that the synthesized compounds have good binding affinity in the binding pockets of AChE, BChE, COX-2, 5-LOX and alpha-amylase enzyme and showed high binding energies. The synthesized succinimide derivatives, i.e. compound 23, 31, 44 showed marked inhibitory activities against cyclooxygenase, lipoxygenase, alpha-amylase and cholinesterase enzymes. Among these three, compound 44 and 31 showed strong anti-inflammatory and anti-diabetic activity while they displayed moderate anti-cholinesterase activity supported by molecular docking results.Communicated by Ramaswamy H. Sarma.
ESTHER : Pervaiz_2022_J.Biomol.Struct.Dyn__1
PubMedSearch : Pervaiz_2022_J.Biomol.Struct.Dyn__1
PubMedID: 35507043

Title : Phytochemical Analysis and Binding Interaction of Cotton Seed Cake Derived Compounds with Target Protein of Meloidogyne incognita for Nematicidal Evaluation - Almutairi_2022_Life.(Basel)_12_
Author(s) : Almutairi FM , Khan A , Ajmal MR , Khan RH , Khan MF , Lal H , Ullah MF , Ahmad F , Ahamad L , Arif H , Ayaz Ahmad M
Ref : Life (Basel) , 12 : , 2022
Abstract : The root-knot nematode Meloidogyne incognita is one of the most damaging plant-parasitic nematodes and is responsible for significant crop losses worldwide. Rising human health and environmental concerns have led to the withdrawal of commonly used chemical nematicides. There has been a tremendous demand for eco-friendly bio-nematicides with beneficial properties to the nematode hosting plants, which encourages the need for alternative nematode management practices. The current study was undertaken to determine the nematicidal potential of cotton seed cake (CSC) against second-stage juvenile (J2) hatching, J2 mortality, and J2 penetration of M. incognita in tomato plants in vitro. J2s and egg masses of M. incognita were exposed to four concentrations (250, 500, 750, and 1000 mg/L) of CSC extracts. The higher J2 mortality and inhibition of J2 hatching were found at 1000 mg/L, while the least effective result was observed at 250 mg/L of the CSC extract. The CSC extract applied with the concentrations mentioned above also showed inhibition of J2 penetration in tomato roots; 1000 mg/L showed the highest inhibition of penetration, while 250 mg/L displayed the least inhibition. Using gas chromatography-mass spectroscopy, we identified 11 compounds, out of which 9,12-Octadecadienoic acid, Hexadecanoic acid, and Tetradecanoic acid were found as major compounds. Subsequently, in silico molecular docking was conducted to confirm the nematicidal behavior of CSC based on binding interactions of the above three major compounds with the targeted protein acetylcholine esterase (AChE) of M. incognita. The values of binding free energy are -5.3, -4.5, and -4.9 kcal/mol, observed for 9,12-Octadecadienoic acid, n-Hexadecanoic acid, and Tetradecanoic acid, respectively, suggesting that 9,12-Octadecadienoic acid binds with the receptor AChE more efficiently than the other two ligands. This study indicates that CSC has nematicidal potential that can be used to control M. incognita for sustainable agriculture.
ESTHER : Almutairi_2022_Life.(Basel)_12_
PubMedSearch : Almutairi_2022_Life.(Basel)_12_
PubMedID: 36556474

Title : In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from Delphinium chitralense - Ahmad_2022_Molecules_27_
Author(s) : Ahmad S , Ahmad M , Almehmadi M , Shah SAA , Khan FA , Khan NM , Khan A , Zainab , Halawi M , Ahmad H
Ref : Molecules , 27 : , 2022
Abstract : This study reports the isolation of three new C(20) diterpenoid alkaloids, Chitralinine A-C (1-3) from the aerial parts of Delphinium chitralense. Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds (1-3) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC(50) value of 11.64 +/- 0.08 microM against AChE, and 24.31 +/- 0.33 microM against BChE, respectively. The molecular docking reflected a binding free energy of -16.400 K Cal-mol(-1) for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer's disease.
ESTHER : Ahmad_2022_Molecules_27_
PubMedSearch : Ahmad_2022_Molecules_27_
PubMedID: 35889221

Title : Potential Cancer- and Alzheimer's Disease-Targeting Phosphodiesterase Inhibitors from Uvaria alba: Insights from In Vitro and Consensus Virtual Screening - Quimque_2021_ACS.Omega_6_8403
Author(s) : Quimque MT , Notarte KI , Letada A , Fernandez RA , Pilapil DYt , Pueblos KR , Agbay JC , Dahse HM , Wenzel-Storjohann A , Tasdemir D , Khan A , Wei DQ , Gose Macabeo AP
Ref : ACS Omega , 6 :8403 , 2021
Abstract : Inhibition of the major cyclic adenosine monophosphate-metabolizing enzyme PDE4 has shown potential for the discovery of drugs for cancer, inflammation, and neurodegenerative disorders such as Alzheimer's disease. As a springboard to explore new anti-cancer and anti-Alzheimer's chemical prototypes from rare Annonaceae species, the present study evaluated anti-PDE4B along with antiproliferative and anti-cholinesterase activities of the extracts of the Philippine endemic species Uvaria alba using in vitro assays and framed the resulting biological significance through computational binding and reactivity-based experiments. Thus, the PDE4 B2B-inhibiting dichloromethane sub-extract (UaD) of U. alba elicited antiproliferative activity against chronic myelogenous leukemia (K-562) and cytostatic effects against human cervical cancer (HeLa). The extract also profoundly inhibited acetylcholinesterase (AChE), an enzyme involved in the progression of neurodegenerative diseases. Chemical profiling analysis of the bioactive extract identified 18 putative secondary metabolites. Molecular docking and molecular dynamics simulations showed strong free energy binding mechanisms and dynamic stability at 50-ns simulations in the catalytic domains of PDE4 B2B, ubiquitin-specific peptidase 14, and Kelch-like ECH-associated protein 1 (KEAP-1 Kelch domain) for the benzylated dihydroflavone dichamanetin (16), and of an AChE and KEAP-1 BTB domain for 3-(3,4-dihydroxybenzyl)-3',4',6-trihydroxy-2,4-dimethoxychalcone (8) and grandifloracin (15), respectively. Density functional theory calculations to demonstrate Michael addition reaction of the most electrophilic metabolite and kinetically stable grandifloracin (15) with Cys151 of the KEAP-1 BTB domain illustrated favorable formation of a beta-addition adduct. The top-ranked compounds also conferred favorable in silico pharmacokinetic properties.
ESTHER : Quimque_2021_ACS.Omega_6_8403
PubMedSearch : Quimque_2021_ACS.Omega_6_8403
PubMedID: 33817501

Title : New multitarget directed benzimidazole-2-thiol-based heterocycles as prospective anti-radical and anti-Alzheimer's agents - Latif_2021_Drug.Dev.Res_82_207
Author(s) : Latif A , Bibi S , Ali S , Ammara A , Ahmad M , Khan A , Al-Harrasi A , Ullah F , Ali M
Ref : Drug Dev Res , 82 :207 , 2021
Abstract : A series of new heterocycles (4-18) was synthesized by the structural modification of benzimidazole-2-thiol (BT, 2-MBI). The structures of the synthesized compounds were confirmed with the help of high-resolution mass spectrometry (HRMS) and (1) HNMR spectroscopy. High inhibitions of the oxidants such as ABTS and DPPH were observed for compounds 9 [IC(50) (s) = 167.4 microM (ABTS), 139.5 microM (DPPH)], 10 [IC(50) (s) = 186.5 microM (ABTS), 155.4 microM (DPPH)], 11 [IC(50) (s) = 286.1 microM (ABTS), 189.1 microM (DPPH)], 12 [IC(50) (s) = 310.8 microM (ABTS), 162.2 microM (DPPH)], 14 [IC(50) (s) = 281.3 microM (ABTS), 205.7 microM (DPPH)], 15 [IC(50) (s) = 284.1 microM (ABTS), 177.3 microM (DPPH)], and 16 [IC(50) (s) = 344.7 microM (ABTS), 270.2 microM (DPPH)] as compared with Ascorbic acid [IC(50) (s) = 340.9 microM (ABTS), 164.3 microM (DPPH)]. The anti-Alzheimer's activity was performed in vitro against cholinesterase enzymes (AChE, BChE). Compound 11 was able to show significant inhibitions [IC(50) (s) = 121.2 microM (AChE), 38.3 microM (BChE)] as against that of galantamine [IC(50) (s) = 139.4 microM (AChE), 40.3 microM (BChE)]. Compound 14 was found as a very good inhibitor of butyrylcholinesterase (IC(50) = 35.4 microM) as compared with standard galantamine. Molecular docking was further performed to investigate the mechanism of anticholinesterase activity.
ESTHER : Latif_2021_Drug.Dev.Res_82_207
PubMedSearch : Latif_2021_Drug.Dev.Res_82_207
PubMedID: 32897587

Title : Identification of novel acetylcholinesterase inhibitors through 3D-QSAR, molecular docking, and molecular dynamics simulation targeting Alzheimer's disease - El Khatabi_2021_J.Mol.Model_27_302
Author(s) : El Khatabi K , El-Mernissi R , Aanouz I , Ajana MA , Lakhlifi T , Khan A , Wei DQ , Bouachrine M
Ref : J Mol Model , 27 :302 , 2021
Abstract : Acetylcholinesterase (AChE) is a potential target for the development of small molecules as inhibitors for the therapy of Alzheimer's disease (AD). To design highly active acetylcholinesterase inhibitors, a three-dimensional quantitative structure-activity relationship (3D-QSAR) approach was performed on a series of N-benzylpyrrolidine derivatives previously evaluated for acetylcholinesterase inhibitory activity. The developed two models, CoMFA and CoMSIA, were statistically validated, and good predictability was achieved for both models. The information generated from 3D-QSAR contour maps may provide a better understanding of the structural features required for acetylcholinesterase inhibition and help to design new potential anti-acetylcholinesterase molecules. Consequently, six novel acetylcholinesterase inhibitors were designed, among which compound A1 with the highest predicted activity was subjected to detailed molecular docking and compared to the most active compound. Extra-precision molecular dynamics (MD) simulation of 50 ns and binding free energy calculations using MM-GBSA were performed for the selected compounds to validate the stability. These results may afford important structural insights needed to identify novel acetylcholinesterase inhibitors and other promising strategies in drug discovery.
ESTHER : El Khatabi_2021_J.Mol.Model_27_302
PubMedSearch : El Khatabi_2021_J.Mol.Model_27_302
PubMedID: 34581863

Title : Bio-Potency and Molecular Docking Studies of Isolated Compounds from Grewia optiva J.R. Drumm. ex Burret - Ul_2021_Molecules_26_
Author(s) : Ul Bari W , Ur Rehman N , Khan A , Ahsan Halim S , Yuan Y , Blaskovich MAT , Ziora ZM , Zahoor M , Naz S , Ullah R , Alotaibi A , Al-Harrasi A
Ref : Molecules , 26 : , 2021
Abstract : In the study, two novel compounds along with two new compounds were isolated from Grewia optiva. The novel compounds have never been reported in any plant source, whereas the new compounds are reported for the first time from the studied plant. The four compounds were characterized as: 5,5,7,7,11,13-hexamethyl-2-(5-methylhexyl)icosahydro-1H-cyclopenta[a]chrysen-9-ol (IX), docosanoic acid (X), methanetriol mano formate (XI) and 2,2'-(1,4-phenylene)bis(3-methylbutanoic acid (XII). The anticholinesterase, antidiabetic, and antioxidant potentials of these compounds were determined using standard protocols. All the isolated compounds exhibited a moderate-to-good degree of activity against acetylcholinesterases (AChE) and butyrylcholinesterase (BChE). However, compound XII was particularly effective with IC(50) of 55 microg/mL (against AChE) and 60 microg/mL (against BChE), and this inhibitory activity is supported by in silico docking studies. The same compound was also effective against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) radicals with IC(50) values of 60 and 62 microg/mL, respectively. The compound also significantly inhibited the activities of alpha-amylase and alpha-glucosidase in vitro. The IC(50) values for inhibition of the two enzymes were recorded as 90 and 92 microg/mL, respectively. The in vitro potentials of compound XII to treat Alzheimer's disease (in terms of AchE and BChE inhibition), diabetes (in terms of alpha-amylase and alpha-glucosidase inhibition), and oxidative stress (in terms of free radical scavenging) suggest further in vivo investigations of the compound for assessing its efficacy, safety profile, and other parameters to proclaim the compound as a potential drug candidate.
ESTHER : Ul_2021_Molecules_26_
PubMedSearch : Ul_2021_Molecules_26_
PubMedID: 33916198

Title : Macrocyclic sulfone derivatives: Synthesis, characterization, in vitro biological evaluation and molecular docking - Ibrahim_2021_Drug.Dev.Res_82_562
Author(s) : Ibrahim M , Latif A , Ammara , Ali A , Ribeiro AI , Farooq U , Ullah F , Khan A , Al-Harrasi A , Ahmad M , Ali M
Ref : Drug Dev Res , 82 :562 , 2021
Abstract : An artificial series of macrocycles based on 4,4'-sulfonyldiphenol intermediate was synthesized using a multistep procedure involving oxidation of bisphenol sulfide, etherification of phenolic hydroxyl groups, and final ring closure with different diamines. Different chemical species having aromatic, heteroaromatic, and aliphatic characters were incorporated into macrocyclic frameworks in the final step of ring closure. This simple and easily executable synthetic strategy was applied to synthesize 15 macrocycles (5a-o) in excellent yields. Characterization of the synthesized products was achieved through well-known modern spectroscopic techniques such as IR, NMR, and Mass. Macrocycles 5m and 5n were found to show significant AChE inhibition with IC(50) values of 76.9+/-0.24 and 71.2+/-0.77microM, respectively. Macrocycle 5n was also found to be an active inhibitor of butyrylcholinesterase (BChE) with IC(50) score of 55.3+/-0.54microM. Among others, macrocycle 5l cyclized with o-phenylenediamine demonstrated moderate inhibition with IC(50) value of 81.1+/-0.54microM. Increasing interest in studying interactions of macrocycles with different enzymatic targets compelled us to design and synthesize sulfone-based macrocycles that might prove as highly potent class of biologically active compounds.
ESTHER : Ibrahim_2021_Drug.Dev.Res_82_562
PubMedSearch : Ibrahim_2021_Drug.Dev.Res_82_562
PubMedID: 33368483

Title : Attenuation of spatial memory in 5xFAD mice by targeting cholinesterases, oxidative stress and inflammatory signaling using 2-(hydroxyl-(2-nitrophenyl)methyl)cyclopentanone - Ullah_2021_Int.Immunopharmacol_100_108083
Author(s) : Ullah R , Ali G , Subhan F , Khan A , Ahsan Halim S , Naveed M , Kalsoom S , Al-Harrasi A
Ref : Int Immunopharmacol , 100 :108083 , 2021
Abstract : Alzheimer's disease (AD) is classified pathologically as a progressive neurological disorder associated with memory decline. The study was designed to assess the underlying molecular signaling involved in the neuroprotective effect of the 2-(hydroxyl-(2-nitrophenyl)methyl)cyclopentanone (2NCP) as a novel therapeutic agent for AD. In this connection, in vitro cholinesterases inhibitory and antioxidant activities were investigated. In vivo studies were carried out on a well-known 5xFAD mice model in different behavioural models such as light/dark box,balance beam, rotarod, elevated plus maze (EPM),novel object recognition (NOR), paddling Y-maze, and Morris water maze (MWM) tests. Hippocampus (HC) and frontal cortex (FC) homogenates were examined for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals, glutathione S-transferase (GST), glutathione (GSH), and catalase. Further, we examined the expression of inflammatory cytokines and Nrf2 in the HC and FC through RT-PCR. Computational studies were conducted to predict the binding mode of the 2NCP with target sites of nuclear factor-kappaB (NF-kappaB) and cholinesterases. The findings of in vitro assays revealed that the IC(50) values of the 2NCP against AChE and BChE were 17 and 23 microg/ml respectively. DPPH antioxidant assay displayed an IC(50) value for the 2NCP was 62 microg/ml. Whereas, theex vivo study depicted that the activities of AChE and BChEwere significantly reduced. Moreover, free radicals load, GSH level, catalase and GST activities were significantly declined. Furthermore, in vivostudies showed that the 2NCP treated animals exhibited gradual memory improvement and improved motor functions. RT-PCR study revealed that mRNA levels of the inflammatory mediators (IL-1beta, IL-6, TNF-alpha) were significantly reduced, while the expression of antioxidant Nrf2 was significantly increased.The molecular docking studies further confirmed that the 2NCP showed excellent binding affinities for NF-kappaB and cholinesterases. Taken together, the 2NCP improves spatial memory and learning, short- and long-term memory,markedly inhibits cholinesterases, reduced neuroinflammation, and mitigated oxidative stress in the 5xFAD mice; hence the 2NCP may be a potential candidate for the management of AD.
ESTHER : Ullah_2021_Int.Immunopharmacol_100_108083
PubMedSearch : Ullah_2021_Int.Immunopharmacol_100_108083
PubMedID: 34478946

Title : Potential therapeutic natural products against Alzheimer's disease with Reference of Acetylcholinesterase - Ahmed_2021_Biomed.Pharmacother_139_111609
Author(s) : Ahmed S , Khan ST , Zargaham MK , Khan AU , Khan S , Hussain A , Uddin J , Khan A , Al-Harrasi A
Ref : Biomed Pharmacother , 139 :111609 , 2021
Abstract : Alzheimer's disease (AD), is the most common type of dementia primarily affecting the later years of life. Its prevalence is likely to increase in any aging population and will be a major burden on healthcare system by the mid of the century. Despite scientific and technological breakthroughs in the last 50 years, that have expanded our understanding of the disease on a system, cellular and molecular level, therapies that could stop or slow the progression of the disease are still unavailable. The Food and Drug Administration (FDA), has approved acetylcholinesterase (AChE) inhibitors (donepezil, galantamine, tacrine and rivastigmine) and glutamate receptor antagonist (memantine) for the treatment of AD. In this review we summarize the studies reporting phytocompounds and extracts from medicinal plants that show AChE inhibitory activities and could be of potential benefit in AD. Future research directions are suggested and recommendations made to expand the use of medicinal plants and their formulations to prevent, mitigate and treat AD.
ESTHER : Ahmed_2021_Biomed.Pharmacother_139_111609
PubMedSearch : Ahmed_2021_Biomed.Pharmacother_139_111609
PubMedID: 33915501

Title : An in silico approach to identify potential medicinal plants for treating Alzheimer disease: a case study with acetylcholinesterase - Potshangbam_2020_J.Biomol.Struct.Dyn__1
Author(s) : Potshangbam AM , Nandeibam A , Amom T , Potshangbam N , Rahaman H , Rathore RS , Singh LR , Khan A
Ref : J Biomol Struct Dyn , :1 , 2020
Abstract : Alzheimer's disease (AD) is a progressive neurological disorder affecting an estimated 10 million people worldwide. There is no cure for AD, and only a handful of drugs are known to provide some relief of the symptoms. The prescription drug donepezil has been widely used to treat to slow the progression and onset of the disease; however, the unpleasant side effects have paved the way to find alternative medicines. Many herbs are known to improve brain function, but evidence of medicinal plants that can treat AD is limited due to the lack of concrete rational evidences. Moreover, the traditional method of randomly screening plant extract against AD targets takes time and resources. In this study, a receptor-based in silico method has been implemented which serves to accelerate the process of identification of medicinal plants useful for treatment of AD. A database of natural compounds was compiled to identify hits against acetylcholinesterase (AChE). Receptor-based pharmacophore screening was performed, and selected hits were subjected to docking and molecular dynamics simulations. Molecular Mechanics/Generalized Born surface area (MM/GBSA) calculations were carried out to identify the best scoring hits further. In vitro assays were done for the plant extracts containing the top-scoring hits against AChE. Three plant extracts showed favorable inhibitory activity. Communicated by Ramaswamy H. Sarma.
ESTHER : Potshangbam_2020_J.Biomol.Struct.Dyn__1
PubMedSearch : Potshangbam_2020_J.Biomol.Struct.Dyn__1
PubMedID: 33021148

Title : Polymethylated acylphloroglucinols from Rhodomyrtus tomentosa exert acetylcholinesterase inhibitory effects - Qin_2020_Bioorg.Chem__104519
Author(s) : Qin XJ , Liu H , Li PP , Ni W , He L , Khan A , Hao XJ , Liu HY
Ref : Bioorg Chem , :104519 , 2020
Abstract : Chemical investigation of the twigs and leaves of Rhodomyrtus tomentosa led to the isolation and structural identification of a novel polymethylated phloroglucinol meroterpenoid (PPM) featuring a 6/6/6/6 tetracyclic system, rhotomentodione F (1), five new polymethylated polycyclic phloroglucinols (PPPs) with a rare bis-furan framework, rhotomentosones A-E (2-6), and one new adduct composed of an acylphloroglucinol and two beta-triketone units, rhotomentosone F (7), as well as five known analogues (8-12). Their structures and absolute configurations were unambiguously determined by comprehensive spectroscopic data and electronic circular dichroism (ECD) calculations. All isolates were evaluated for their anti-inflammatory and acetylcholinesterase (AChE) inhibitory activities. Compound 6 displayed significant AChE inhibitory effect with an IC(50) value of 8.68 M. Further molecular docking studies of 6 revealed that the interactions with AChE residues Ser125, Glu202, and Tyr133 are crucial for AChE inhibitory activity. The current study not only enriches the chemical diversity of phloroglucinols in Myrtaceae species, but also provides potential lead compounds for the further design and development of new AChE inhibitors to treat Alzheimer's disease.
ESTHER : Qin_2020_Bioorg.Chem__104519
PubMedSearch : Qin_2020_Bioorg.Chem__104519
PubMedID: 33293058

Title : The potential of Allium sativum and Cannabis sativa extracts for anti-tick activities against Rhipicephalus (Boophilus) microplus - Nasreen_2020_Exp.Appl.Acarol_82_281
Author(s) : Nasreen N , Niaz S , Khan A , Zaman MA , Ayaz S , Naeem H , Khan N , Elgorban AM
Ref : Exp Appl Acarol , 82 :281 , 2020
Abstract : The efficacy of Allium sativum and Cannabis sativa against Rhipicephalus microplus ticks was evaluated using the adult immersion and the larval packet test. In addition, an in silico approach was utilized by performing a docking study in order to identify the active ingredients from both plants. Results showed a comparatively high lethal effect of A. sativum and C. sativa on egg laying (index of egg laying=0.26 and 0.24, respectively), egg hatching (33.5 and 37.1, respectively), and total larval mortality (100%, both), at 40 mg/mL. When applied to cattle which had been inoculated with larvae ticks, it was observed that a 45% solution of both herbal extracts significantly reduced the number of ticks by 96 h post treatment. We analyzed in silico 27 known active molecules from both plants and identified in the PubChem database to explore the hypothesis that the effect found on ticks was based on inhibition of acetylcholinesterase (AChE). Vitamin E and cannabidiol are the most potent AChE inhibitors with docking scores of -15.85 and -14.38, respectively. Based on these findings, we conclude that A. sativum and C. sativa may potentially be used for the control of R. microplus, and should be further investigated as a potential supplement to or replacement of synthetic acaricides.
ESTHER : Nasreen_2020_Exp.Appl.Acarol_82_281
PubMedSearch : Nasreen_2020_Exp.Appl.Acarol_82_281
PubMedID: 32886258

Title : Synthesis, characterization, molecular docking evaluation, antidepressant, and anti-Alzheimer effects of dibenzylidene ketone derivatives - Bashir_2019_Drug.Dev.Res_80_595
Author(s) : Bashir MA , Khan AU , Badshah H , Rodrigues-Filho E , Din ZU , Khan A
Ref : Drug Dev Res , 80 :595 , 2019
Abstract : Novel bioactive compounds as synthetic analogs of the potent herbal medicines can be optimized as potential drug candidates for various neurologic disorders. This study was performed to investigate the newly synthesized dibenzylidene ketone derivatives: (2E,6E)-2,6-dibenzylidene cyclohexanone (A1K1) and (1E,4E)-5-(2,3-dichlorophenyl)-1-(4-methoxyphenyl)-2-methylpenta-1,4-diene-3-one (A2K2) and evaluate its potential anti-Alzheimer's and anti-depressant properties. Both the derivatives are chemically characterized by using HNMR and CNMR techniques. Auto Dock Vina program was used to investigate ligand-protein affinity. Forced swim test, tail suspension test, open field test, Y-maze test, and Morris water maze test (MWM) models were employed to evaluate anti-depressant and anti-Alzheimer's activity of dibenzylidene ketone derivatives in mice. Both A1K1 and A2K2 showed high binding affinities against various proteins involved in depression and Alzheimer's mechanisms like monoamine oxidase B, acetylcholinesterase, norepinephrine transporter 2, serotonin transporter, dopamine receptor, serotonin receptor modulator, and beta-amyloid targets. A1K1 and A2K2 dose-dependently (0.1-1 mg/kg) decreased immobility time, while increased swimming and climbing time of mice in forced swim test (FST). A1K1 and A2K2 decreased animal immobility time in TST. In the open field test, both A1K1 and A2K2 increased the number of ambulations and rearings. A1K1 and A2K2 dose-dependently (0.5-1.0 mg/kg) increased spontaneous alternation behavior (%) and the number of entries of mice in Y-maze test. In the MWM test, A1K1 and A2K2 decreased escape latency time. Overall, both in-silico and in-vivo investigations of A1K1 and A2K2, report their therapeutic potential for antidepressant and anti-Alzheimer properties. Hence, these compounds possess potent neuroprotective properties and may be further evaluated for their therapeutic potential in various neurological disorders.
ESTHER : Bashir_2019_Drug.Dev.Res_80_595
PubMedSearch : Bashir_2019_Drug.Dev.Res_80_595
PubMedID: 30964563

Title : Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and Pharmacokinetics of Coumarinyl Thiazoles and Oxadiazoles - Ibrar_2018_Front.Chem_6_61
Author(s) : Ibrar A , Khan A , Ali M , Sarwar R , Mehsud S , Farooq U , Halimi SMA , Khan I , Al-Harrasi A
Ref : Front Chem , 6 :61 , 2018
Abstract : In a continuation of our previous work for the exploration of novel enzyme inhibitors, two new coumarin-thiazole 6(a-o) and coumarin-oxadiazole 11(a-h) hybrids have been designed and synthesized. All the compounds were characterized by (1)H- and (13)C-NMR spectroscopy and elemental analysis. New hybrid analogs were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in order to know their potential for the prevention of Alzheimer's disease (AD). In coumarinyl thiazole series, compound 6b was found as the most active member against AChE having IC50 value of 0.87 +/- 0.09 muM, while the compound 6j revealed the same efficacy against BuChE with an IC50 value of 11.01 +/- 3.37 muM. In case of coumarinyl oxadiazole series, 11a was turned out to be the lead candidate against AChE with an IC50 value of 6.07 +/- 0.23 muM, whereas compound 11e was found significantly active against BuChE with an IC50 value of 0.15 +/- 0.09 muM. To realize the binding interaction of these compounds with AChE and BuChE, the molecular docking studies were performed. Compounds from coumarinyl thiazole series with potent AChE activity (6b, 6h, 6i, and 6k) were found to interact with AChE in the active site with MOE score of -10.19, -9.97, -9.68, and -11.03 Kcal.mol(-1), respectively. The major interactions include hydrogen bonding, pi-pi stacking with aromatic residues, and interaction through water bridging. The docking studies of coumarinyl oxadiazole derivatives 11(a-h) suggested that the compounds with high anti-butyrylcholinesterase activity (11e, 11a, and 11b) provided MOE score of -9.9, -7.4, and -8.2 Kcal.mol(-1), respectively, with the active site of BuChE building pi-pi stacking with Trp82 and water bridged interaction.
ESTHER : Ibrar_2018_Front.Chem_6_61
PubMedSearch : Ibrar_2018_Front.Chem_6_61
PubMedID: 29632858

Title : Two new prenylated C6-C3 compounds from Illicium micranthum Dunn - Liu_2018_Nat.Prod.Res__1
Author(s) : Liu L , Lv XM , Hua T , Khan A , Huang XB , Wang YF , Zhou ZH
Ref : Nat Prod Res , :1 , 2018
Abstract : Phytochemical investigation of Illicium micranthum led to the isolation of two new prenylated C6-C3 compounds, 12-O-methyl-2,3-dehydroillifunone C (1) and illiciminone A (2), together with three known analogues (3-5) and one known sesquiterpene lactone (6). The structures were established by extensive spectroscopic characterization and the reported data. All the isolates were evaluated for their acetylcholinesterase (AChE) inhibition activity. Compound 5 showed weak inhibitory activity (46.0%) at 50 muM concentration.
ESTHER : Liu_2018_Nat.Prod.Res__1
PubMedSearch : Liu_2018_Nat.Prod.Res__1
PubMedID: 30450961

Title : Neurologically Potent Molecules from Crataegus oxyacantha\; Isolation, Anticholinesterase Inhibition, and Molecular Docking - Ali_2017_Front.Pharmacol_8_327
Author(s) : Ali M , Muhammad S , Shah MR , Khan A , Rashid U , Farooq U , Ullah F , Sadiq A , Ayaz M , Ahmad M , Latif A
Ref : Front Pharmacol , 8 :327 , 2017
Abstract : Crataegus oxyacantha is an important herbal supplement and famous for its antioxidant potential. The antioxidant in combination with anticholinesterase activity can be considered as an important target in the management of Alzheimer's disease. The compounds isolated from C. oxyacantha were evaluated for cholinesterases inhibitory activity using Ellman's assay with Galantamine as standard drug. Total of nine (1-9) compounds were isolated. Compounds 1 and 2 were isolated for the first time from natural source. Important natural products like beta-Sitosterol-3-O-beta-D-Glucopyranoside (3), lupeol (4), beta-sitosterol (5), betulin (6), betulinic acid (7), oleanolic acid (8), and chrysin (9) have also been isolated from C. oxyacantha. Overall, all the compounds exhibited an overwhelming acetylcholinesterase (AChE) inhibition potential in the range 5.22-44.47 muM. The compound 3 was prominent AChE inhibitor with IC50 value of 5.22 muM. Likewise, all the compounds were also potent in butyrylcholinesterase (BChE) inhibitions with IC50s of up to 0.55-15.36 muM. All the compounds, except 3, were selective toward BChE. Mechanism of the inhibition of both the enzymes were further studied by docking procedures using Genetic Optimization for Ligand Docking suit v5.4.1. Furthermore, computational blood brain barrier prediction of the isolated compounds suggest that these are BBB+.
ESTHER : Ali_2017_Front.Pharmacol_8_327
PubMedSearch : Ali_2017_Front.Pharmacol_8_327
PubMedID: 28638340

Title : Sequence variants in nine different genes underlying rare skin disorders in 10 consanguineous families - Shah_2017_Int.J.Dermatol_56_1406
Author(s) : Shah K , Mehmood S , Jan A , Abbe I , Hussain Ali R , Khan A , Chishti MS , Lee K , Ahmad F , Ansar M , Shahzad S , Nickerson DA , Bamshad MJ , Coucke PJ , Santos-Cortez RLP , Spritz RA , Leal SM , Ahmad W
Ref : Int J Dermatol , 56 :1406 , 2017
Abstract : BACKGROUND: Genodermatoses represent genetic anomalies of skin tissues including hair follicles, sebaceous glands, eccrine glands, nails, and teeth. Ten consanguineous families segregating various genodermatosis phenotypes were investigated in the present study. METHODS: Homozygosity mapping, exome, and Sanger sequencing were employed to search for the disease-causing variants in the 10 families. RESULTS: Exome sequencing identified seven homozygous sequence variants in different families, including: c.27delT in FERMT1; c.836delA in ABHD5; c.2453C>T in ERCC5; c.5314C>T in COL7A1; c.1630C>T in ALOXE3; c.502C>T in PPOX; and c.10G>T in ALDH3A2. Sanger sequencing revealed three homozygous variants: c.1718 + 2A>G in FERMT1; c.10459A>T in FLG; and c.92delT in the KRT14 genes as the underlying genetic cause of skin phenotypes. CONCLUSION: This study supports the use of exome sequencing as a powerful, efficient tool for identifying genes that underlie rare monogenic skin disorders.
ESTHER : Shah_2017_Int.J.Dermatol_56_1406
PubMedSearch : Shah_2017_Int.J.Dermatol_56_1406
PubMedID: 29130490
Gene_locus related to this paper: human-ABHD5

Title : Pistagremic acid, a novel beta-secretase enzyme (BACE1) inhibitor from Pistacia integerrima Stewart - Rauf_2015_Nat.Prod.Res_29_1735
Author(s) : Rauf A , Uddin G , Khan A , Siddiqui BS , Arfan M , Dalvandi K , Ben Hadda T
Ref : Nat Prod Res , 29 :1735 , 2015
Abstract : A new triterpenic compound named pistagremic acid (PA) was once again isolated from Pistaciaintegerrima. The beta-secretase inhibition study was carried out. Compound PA was found significantly active against beta-secretase enzyme (BACE1) with IC50 value of 350 +/- 2 nM in comparison to the standard inhibitors [Asn670, Sta671, Val672]-amyloid-beta/A4 precursor protein 770 fragment 662-675 (IC50 = 290.71 +/- 1 nM). The selectivity of this compound was also evaluated against the acetylcholinesterase and butyrylcholinesterase enzymes. Interestingly compound PA was found to be inactive against them and showed selectivity towards beta-secretase enzyme (BACE1).
ESTHER : Rauf_2015_Nat.Prod.Res_29_1735
PubMedSearch : Rauf_2015_Nat.Prod.Res_29_1735
PubMedID: 25588845

Title : Complete Genome Sequence of Martelella endophytica YC6887, Which Has Antifungal Activity Associated with a Halophyte - Khan_2015_Genome.Announc_3_
Author(s) : Khan A , Khan H , Chung EJ , Hossain MT , Chung YR
Ref : Genome Announc , 3 : , 2015
Abstract : Martelella endophytica YC6887, which produces antifungal compounds against fungal and oomycete pathogens, was isolated from the root of a halophyte, Rosa rugosa, collected at a tidal flat in South Korea. Its full-genome sequence shows that it is a circular DNA, without a plasmid, of about 4.8 Mb in size.
ESTHER : Khan_2015_Genome.Announc_3_
PubMedSearch : Khan_2015_Genome.Announc_3_
PubMedID: 25953177
Gene_locus related to this paper: 9rhiz-a0a0d5lrg3

Title : Report: Screening of selected medicinal plants for their enzyme inhibitory potential - A validation of their ethnopharmacological uses - Khuda_2014_Pak.J.Pharm.Sci_27_593
Author(s) : Khuda F , Iqbal Z , Khan A , Zakiullah , Shah Y
Ref : Pak J Pharm Sci , 27 :593 , 2014
Abstract : In present study four medicinal plants namely Valeriana wallichii, Xanthium strumarium, Achyranthes aspera and Duchesnea indica belonging to different families were collected in Khyber Pakhtunkhwa province and crude extract and subsequent fractions were analyzed for their inhibitory potential against acetylcholinesterase, butyrylcholinesterase and alpha-glucosidase enzymes. Valeriana wallichii, Xanthium strumarium and Achyranthes aspera were significantly active against cholinesterases. Chloroform and ethylacetate fractions of Valeriana wallichii exhibited significant activity against acetylcholinesterase (IC50: 61mug/ml) and butyrylcholinesterase enzymes (IC50: 58mug/ml), respectively. Similarly ethylacetate fraction of Achyranthes aspera showed significant activity against acetylcholinesterase (IC50: 61 mug/ml) and butyrylcholinesterase enzymes (IC50: 61 mug/ml), respectively. In case of alpha-glucosidase enzyme, the chloroform fraction of Xanthium strumarium exhibited significant inhibitory activity (IC50: 72 mug/ml) as compared to the standard compound acarbose (IC50: 483 mug/ml). Duchesnea indica showed no such activities.
ESTHER : Khuda_2014_Pak.J.Pharm.Sci_27_593
PubMedSearch : Khuda_2014_Pak.J.Pharm.Sci_27_593
PubMedID: 24811822

Title : Synthesis and bioactivities of silver nanoparticles capped with 5-Amino-ss-resorcylic acid hydrochloride dihydrate - Naz_2014_J.Nanobiotechnology_12_34
Author(s) : Naz S , Shah M , Islam N , Khan A , Nazir S , Qaisar S , Alam S
Ref : J Nanobiotechnology , 12 :34 , 2014
Abstract : BackgroundConjugated and drug loaded silver nanoparticles are getting an increased attention for various biomedical applications. Nanoconjugates showed significant enhancement in biological activity in comparison to free drug molecules. In this perspective, we report the synthesis of bioactive silver capped with 5-Amino-ss-resorcylic acid hydrochloride dihydrate (AR). The in vitro antimicrobial (antibacterial, antifungal), enzyme inhibition (xanthine oxidase, urease, carbonic anhydrase, inverted question mark-chymotrypsin, cholinesterase) and antioxidant activities of the developed nanostructures was investigated before and after conjugation to silver metal.ResultsThe conjugation of AR to silver was confirmed through FTIR, UV inverted question markvis and TEM techniques. The amount of AR conjugated with silver was characterized through UV inverted question markvis spectroscopy and found to be 9% by weight. The stability of synthesized nanoconjugates against temperature, high salt concentration and pH was found to be good. Nanoconjugates, showed significant synergic enzyme inhibition effect against xanthine and urease enzymes in comparison to standard drugs, pure ligand and silver.ConclusionsOur synthesized nanoconjugate was found be to efficient selective xanthine and urease inhibitors in comparison to Ag and AR. On a per weight basis, our nanoconjugates required less amount of AR (about 11 times) for inhibition of these enzymes.
ESTHER : Naz_2014_J.Nanobiotechnology_12_34
PubMedSearch : Naz_2014_J.Nanobiotechnology_12_34
PubMedID: 25201390

Title : Atypical juvenile neuronal ceroid lipofuscinosis: A report of three cases - Setty_2013_J.Pediatr.Neurosci_8_117
Author(s) : Setty G , Saleem R , Khan A , Hussain N
Ref : J Pediatr Neurosci , 8 :117 , 2013
Abstract : The diagnosis of juvenile neuronal ceroid lipofuscinosis (JNCL) is usually based on age of onset, initial clinical symptoms, clinical progression, and pathologic findings. Our cases manifested atypical clinical symptomatology and/or pathologic findings and therefore, represent variant forms of JNCL. Case 1 and 2 presented with slow developmental regression from the age of 4 years and became blind and wheelchair bound at around 8 years. Pathologic finding of lymphocytes showed fingerprint inclusion which was consistent with JNCL. Mutational analysis was positive for CLN5 which usually presents as variant late infantile NCL (LINCL) and more common in Finnish population. Case 3 presented with progressive visual loss from the age of 8 years. Clinical symptomatology and age of onset were similar to that of JNCL but was found to have low palmitoyl protein thioesterase, granular inclusion body, and CLN1 mutation, thus representing milder form of INCL. These three cases demonstrated phenotypic-genotypic variations. Pertinent issues relating diagnostic difficulties, ophthalmologic, neuroradiological, and laboratory aspects are discussed.
ESTHER : Setty_2013_J.Pediatr.Neurosci_8_117
PubMedSearch : Setty_2013_J.Pediatr.Neurosci_8_117
PubMedID: 24082928
Gene_locus related to this paper: human-PPT1

Title : Genome characterization of a novel Burkholderia cepacia complex genomovar isolated from dieback affected mango orchards - Khan_2013_World.J.Microbiol.Biotechnol_29_2033
Author(s) : Khan A , Asif H , Studholme DJ , Khan IA , Azim MK
Ref : World J Microbiol Biotechnol , 29 :2033 , 2013
Abstract : We characterized the genome of the antibiotic resistant, caseinolytic and non-hemolytic Burkholderia sp. strain TJI49, isolated from mango trees (Mangifera indica L.) with dieback disease. This isolate produced severe disease symptoms on the indicator plants. Next generation DNA sequencing and short-read assembly generated the 60X deep 7,631,934 nucleotide draft genome of Burkholderia sp. TJI49 which comprised three chromosomes and at least one mega plasmid. Genome annotation studies revealed a total 8,992 genes, out of which 8,940 were protein coding genes. Comparative genomics and phylogenetics identified Burkholderia sp. TJI49 as a distinct species of Burkholderia cepacia complex (BCC), closely related to B. multivorans ATCC17616. Genome-wide sequence alignment of this isolate with replicons of BCC members showed conservation of core function genes but considerable variations in accessory genes. Subsystem-based gene annotation identified the active presence of wide spread colonization island and type VI secretion system in Burkholderia sp. TJI49. Sequence comparisons revealed (a) 28 novel ORFs that have no database matches and (b) 23 ORFs with orthologues in species other than Burkholderia, indicating horizontal gene transfer events. Fold recognition of novel ORFs identified genes encoding pertactin autotransporter-like proteins (a constituent of type V secretion system) and Hap adhesion-like proteins (involved in cell-cell adhesion) in the genome of Burkholderia sp. TJI49. The genomic characterization of this isolate provided additional information related to the 'pan-genome' of Burkholderia species.
ESTHER : Khan_2013_World.J.Microbiol.Biotechnol_29_2033
PubMedSearch : Khan_2013_World.J.Microbiol.Biotechnol_29_2033
PubMedID: 23653265
Gene_locus related to this paper: 9burk-a0u8m3 , 9burk-f0g8l1

Title : Novel CLN1 mutation with atypical juvenile neuronal ceroid lipofuscinosis - Khan_2013_J.Pediatr.Neurosci_8_49
Author(s) : Khan A , Chieng KS , Baheerathan A , Hussain N , Gosalakkal J
Ref : J Pediatr Neurosci , 8 :49 , 2013
Abstract : We detected a novel CLN1 gene mutation (p.Arg151X, heterogenous) in a 12-year-old boy. Low level of palmitoyl protein thioesterase and granular inclusion pattern in lymphocytes were also consistent with infantile Neuronal ceroid lipofuscinosis (INCL). However, the clinical phenotype was that of atypical juvenile neuronal ceroid lipofuscinosis (JNCL) and consisted of progressive visual loss from the age of 8 years. His visual acuity was 6/60 in both eyes at first presentation, 6/36 one month later, then 6/6 (right eye), and 6/60 (left eye) 6 months later. However, after 4 months, visual acuity dropped to 6/60 in both eyes and at last follow-up, it was 6/60 (right eye) and 3/60 (left eye). Visual hallucinations were also reported. Persistent normal fundi findings, normal electroretinogram (ERG), and delayed visual evoked potentials (VEP) were suggestive of non-retinal adolescence form/atypical JNCL. Visual loss in JNCL is secondary to retinal dystrophy. Our observations suggest that JNCL should be considered in any children presenting with bilateral progressive visual loss even with normal fundi and/or delayed VEP. Electron microscopy of buffy coat and palmitoyl protein thioesterase enzyme study are useful tools in diagnosis. Pertinent issues regarding clinical symptomatology, ophthalmologic findings, and laboratory results are discussed.
ESTHER : Khan_2013_J.Pediatr.Neurosci_8_49
PubMedSearch : Khan_2013_J.Pediatr.Neurosci_8_49
PubMedID: 23772246

Title : Taurine ameliorates neurobehavioral, neurochemical and immunohistochemical changes in sporadic dementia of Alzheimer's type (SDAT) caused by intracerebroventricular streptozotocin in rats - Javed_2013_Neurol.Sci_34_2181
Author(s) : Javed H , Khan A , Vaibhav K , Moshahid Khan M , Ahmad A , Ejaz Ahmad M , Tabassum R , Islam F , Safhi MM
Ref : Neurol Sci , 34 :2181 , 2013
Abstract : Oxidative loads in the brain are involved in age related impairments like learning and memory as well as neurodegeneration. Taurine, the most abundant free amino acid in humans has many potential health benefits through its anti-oxidant and anti-inflammatory properties. Therefore, we investigated the neuroprotective potential of taurine on oxidative stress, neuronal loss and memory impairments in streptozotocin model of cognitive impairments in rats. The cognitive impairment was developed by giving single intracerebroventricular (ICV) injection of streptozotocin (STZ) 3 mg/kg body weight bilaterally. An increased latency and path length was observed in ICV-STZ group animals as compared to sham group animals and these were inhibited significantly in STZ group pre-treated with taurine (50 mg/kg body weight orally once daily for 15 days). Moreover, the significantly depleted content of GSH and elevated level of thiobarbituric acid reactive substances (TBARS) in ICV-STZ group animals were protected significantly with pre-treatment of taurine. The activity of antioxidant enzymes, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, catalase, and superoxide dismutase was decreased in STZ group as compared to sham group and pre-treatment of STZ group with taurine has protected their activities significantly. Furthermore, the increased activity of acetylcholine esterase and decreased expression of choline acetyl transferase were attenuated by the pre-treatment of taurine. Taurine also protected the morphology of the hippocampal pyramidal neurons. This study concludes that the prophylactic intervention of taurine may be used to prevent the deterioration of cognitive functions and neurobehavioral activities, often associated with the generation of free radicals.
ESTHER : Javed_2013_Neurol.Sci_34_2181
PubMedSearch : Javed_2013_Neurol.Sci_34_2181
PubMedID: 23681104

Title : Multienzyme microbiosensor based on electropolymerized o-phenylenediamine for simultaneous in vitro determination of acetylcholine and choline - Khan_2012_Biosens.Bioelectron_31_433
Author(s) : Khan A , Ab Ghani S
Ref : Biosensors & Bioelectronics , 31 :433 , 2012
Abstract : The electrochemical biosensors based on poly(o-phenylenediamine) (PoPD) and acetylcholinesterase (AChE) and choline oxidase (ChO) enzymes were fabricated on carbon fibre (CF) substrate. The electropolymerized PoPD was used to reduce the interfering substances. The electrode assembly was completed by depositing functionalized carbon nano tubes (FCNTs) and Nafion (Naf). Amperometric detection of acetylcholine (ACh) and choline (Ch) were realized at an applied potential of +750 mV vs Ag/AgCl (saturated KCl). At pH 7.4, the final assembly, Naf-FCNTs/AChE-ChO((10:1))/PoPD/CF(Elip), was observed to have high sensitivity towards Ch (6.3+/-0.3 muA mM(-1)) and ACh (5.8+/-0.3 muA mM(-1)), linear range for Ch (K(M)=0.52+/-0.03 mM) and ACh (K(M)=0.59+/-0.07 mM), and for Ch the highest ascorbic acid blocking capacity (97.2+/-2 1mM AA). It had a response time of <5s and with 0.045 muM limit of detection. Studies on different ratio (ACh/Ch) revealed that 10:1, gave best overall response.
ESTHER : Khan_2012_Biosens.Bioelectron_31_433
PubMedSearch : Khan_2012_Biosens.Bioelectron_31_433
PubMedID: 22154168

Title : Effect of secondhand smoke on occupancy of nicotinic acetylcholine receptors in brain - Brody_2011_Arch.Gen.Psychiatry_68_953
Author(s) : Brody AL , Mandelkern MA , London ED , Khan A , Kozman D , Costello MR , Vellios EE , Archie MM , Bascom R , Mukhin AG
Ref : Arch Gen Psychiatry , 68 :953 , 2011
Abstract : CONTEXT: Despite progress in tobacco control, secondhand smoke (SHS) exposure remains prevalent worldwide and is implicated in the initiation and maintenance of cigarette smoking. OBJECTIVE: To determine whether moderate SHS exposure results in brain alpha(4)beta(2)* nicotinic acetylcholine receptor (nAChR) occupancy. Design, Setting, and PARTICIPANTS: Positron emission tomography scanning and the radiotracer 2-[18F]fluoro-3-(2(S)azetidinylmethoxy) pyridine (also known as 2-[(18)F]fluoro-A-85380, or 2-FA) were used to determine alpha(4)beta(2)* nAChR occupancy from SHS exposure in 24 young adult participants (11 moderately dependent cigarette smokers and 13 nonsmokers). Participants underwent two bolus-plus-continuous-infusion 2-FA positron emission tomography scanning sessions during which they sat in the passenger's seat of a car for 1 hour and either were exposed to moderate SHS or had no SHS exposure. The study took place at an academic positron emission tomography center. Main Outcome Measure Changes induced by SHS in 2-FA specific binding volume of distribution as a measure of alpha(4)beta(2)* nAChR occupancy.
RESULTS: An overall multivariate analysis of variance using specific binding volume of distribution values revealed a significant main effect of condition (SHS vs control) (F(1,22) = 42.5, P < .001) but no between-group (smoker vs nonsmoker) effect. Exposure to SHS led to a mean 19% occupancy of brain alpha(4)beta(2)* nAChRs (1-sample t test, 2-tailed, P < .001). Smokers had both a mean 23% increase in craving with SHS exposure and a correlation between thalamic alpha(4)beta(2)* nAChR occupancy and craving alleviation with subsequent cigarette smoking (Spearman rho = -0.74, P = .01).
CONCLUSIONS: Nicotine from SHS exposure results in substantial brain alpha(4)beta(2)* nAChR occupancy in smokers and nonsmokers. Study findings suggest that such exposure delivers a priming dose of nicotine to the brain that contributes to continued cigarette use in smokers. This study has implications for both biological research into the link between SHS exposure and cigarette use and public policy regarding the need to limit SHS exposure in cars and other enclosed spaces.
ESTHER : Brody_2011_Arch.Gen.Psychiatry_68_953
PubMedSearch : Brody_2011_Arch.Gen.Psychiatry_68_953
PubMedID: 21536968

Title : Common inheritance of chromosome Ia associated with clonal expansion of Toxoplasma gondii - Khan_2006_Genome.Res_16_1119
Author(s) : Khan A , Bohme U , Kelly KA , Adlem E , Brooks K , Simmonds M , Mungall K , Quail MA , Arrowsmith C , Chillingworth T , Churcher C , Harris D , Collins M , Fosker N , Fraser A , Hance Z , Jagels K , Moule S , Murphy L , O'Neil S , Rajandream MA , Saunders D , Seeger K , Whitehead S , Mayr T , Xuan X , Watanabe J , Suzuki Y , Wakaguri H , Sugano S , Sugimoto C , Paulsen I , Mackey AJ , Roos DS , Hall N , Berriman M , Barrell B , Sibley LD , Ajioka JW
Ref : Genome Res , 16 :1119 , 2006
Abstract : Toxoplasma gondii is a globally distributed protozoan parasite that can infect virtually all warm-blooded animals and humans. Despite the existence of a sexual phase in the life cycle, T. gondii has an unusual population structure dominated by three clonal lineages that predominate in North America and Europe, (Types I, II, and III). These lineages were founded by common ancestors approximately10,000 yr ago. The recent origin and widespread distribution of the clonal lineages is attributed to the circumvention of the sexual cycle by a new mode of transmission-asexual transmission between intermediate hosts. Asexual transmission appears to be multigenic and although the specific genes mediating this trait are unknown, it is predicted that all members of the clonal lineages should share the same alleles. Genetic mapping studies suggested that chromosome Ia was unusually monomorphic compared with the rest of the genome. To investigate this further, we sequenced chromosome Ia and chromosome Ib in the Type I strain, RH, and the Type II strain, ME49. Comparative genome analyses of the two chromosomal sequences revealed that the same copy of chromosome Ia was inherited in each lineage, whereas chromosome Ib maintained the same high frequency of between-strain polymorphism as the rest of the genome. Sampling of chromosome Ia sequence in seven additional representative strains from the three clonal lineages supports a monomorphic inheritance, which is unique within the genome. Taken together, our observations implicate a specific combination of alleles on chromosome Ia in the recent origin and widespread success of the clonal lineages of T. gondii.
ESTHER : Khan_2006_Genome.Res_16_1119
PubMedSearch : Khan_2006_Genome.Res_16_1119
PubMedID: 16902086
Gene_locus related to this paper: toxgo-q1jt22

Title : Three new cholinesterase-inhibiting cis-clerodane diterpenoids from Otostegia limbata - Ahmad_2005_Chem.Pharm.Bull.(Tokyo)_53_378
Author(s) : Ahmad VU , Khan A , Farooq U , Kousar F , Khan SS , Nawaz SA , Abbasi MA , Choudhary MI
Ref : Chem Pharm Bull (Tokyo) , 53 :378 , 2005
Abstract : Three new tricyclic cis-clerodane type diterpenoids trivially named as limbatolide A (1), limbatolide B (2) and limbatolide C (3) have been isolated from the roots of Otostegia limbata along with two known compounds; oleanic acid and beta-sitosterol. The structure elucidation of the new compounds was based primarily on two-dimensional (2D) NMR techniques. Compounds 1-3 displayed inhibitory potential in a concentration-dependent manner against acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8) enzymes, respectively.
ESTHER : Ahmad_2005_Chem.Pharm.Bull.(Tokyo)_53_378
PubMedSearch : Ahmad_2005_Chem.Pharm.Bull.(Tokyo)_53_378
PubMedID: 15802835