Jan MS

References (13)

Title : Hypoglycemic, anti-inflammatory, and neuroprotective potentials of crude methanolic extract from Acacia nilotica L. - results of an in vitro study - Rauf_2024_Food.Sci.Nutr_12_3483
Author(s) : Rauf A , Ibrahim M , AlOmar TS , Almasoud N , Khalil AA , Khan M , Khalid A , Jan MS , Formanowicz D , Quradha MM
Ref : Food Sci Nutr , 12 :3483 , 2024
Abstract : Acacia nilotica L., also known as babul, belonging to the Fabaceae family and the Acacia genus, is typically used for ornamental purposes and also as a medicinal plant found in tropical and subtropical areas. This plant is a rich source of bioactive compounds. The current study aimed to elucidate the hypoglycemic, anti-inflammatory, and neuroprotective potential of A.nilotica's crude methanolic extract. The results of the in vitro antidiabetic assay revealed that methanolic extract of A.nilotica inhibited the enzyme alpha-glucosidase (IC(50): 33microgmL(-1)) and alpha-amylase (IC(50): 17microgmL(-1)) in a dose-dependent manner. While in the anticholinesterase enzyme inhibitory assay, maximum inhibition was shown by the extract against acetylcholinesterase (AChE) (637.01microgmL(-1)) and butyrylcholinesterase (BChE) (491.98microgmL(-1)), with the highest percent inhibition of 67.54% and 71.50% at 1000microgmL(-1), respectively. This inhibitory potential was lower as compared to the standard drug Galantamine that exhibited 82.43 and 89.50% inhibition at the same concentration, respectively. Moreover, the methanolic extract of A.nilotica also significantly inhibited the activities of cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) in a concentration-dependent manner. The percent inhibitory activity of 5-LOX and COX-2 ranged from 42.47% to 71.53% and 43.48% to 75.22%, respectively. Furthermore, in silico, in vivo, and clinical investigations must be planned to validate the above-stated bioactivities of A.nilotica.
ESTHER : Rauf_2024_Food.Sci.Nutr_12_3483
PubMedSearch : Rauf_2024_Food.Sci.Nutr_12_3483
PubMedID: 38726429

Title : Evaluation of pyrimidine\/pyrrolidine-sertraline based hybrids as multitarget anti-Alzheimer agents: In-vitro, in-vivo, and computational studies - Javed_2023_Biomed.Pharmacother_159_114239
Author(s) : Javed MA , Jan MS , Shbeer AM , Al-Ghorbani M , Rauf A , Wilairatana P , Mannan A , Sadiq A , Farooq U , Rashid U
Ref : Biomed Pharmacother , 159 :114239 , 2023
Abstract : Alzheimer's disease (AD) is a complex, multifactorial and most prevalent progressive neurodegenerative ailment. Its multifactorial and complex nature causes the lack of disease modifying drugs. Hence, multi-target drug design strategies have been adopted to halt the progression of AD. In current research, we applied multitarget strategy to tackle multifactorial nature of AD. Rational design and synthesis of framework of hybrids containing Pyrimidine/pyrrolidine-sertraline scaffolds were carried out. The synthesized compounds were further evaluated for their in-vitro enzyme inhibition potential against cholinesterases, monoamine oxidases and beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1). Compound 19 emerged as an optimal multipotent hybrid with IC(50) values of 0.07smicroM, 0.09smicroM, 0.63smicroM, 0.21smicroM and 0.73smicroM against AChE, BChE, MAO-A, MAO-B and BACE-1 respectively. After in-vivo cytotoxicity and in-vitro PAMPA blood brain barrier permeation assays, a number of widely used behavioral assessment tests were also performed for the evaluation of memory and learning.Determination of biochemical parameters showed low levels of acetylcholinesterase by the treatment with synthesized compounds. Furthermore, levels of neurotransmitters such as serotonin, dopamine and noradrenaline were also analyzed. Increased neurotransmitter levels showed the improved short and long-term memory as well as enhanced learning behavior. Docking studies on the target enzymes showed correlation with the experimental in-vitro enzyme inhibition results.
ESTHER : Javed_2023_Biomed.Pharmacother_159_114239
PubMedSearch : Javed_2023_Biomed.Pharmacother_159_114239
PubMedID: 36638595

Title : Pharmacological evaluations of amide carboxylates as potential anti-Alzheimer agents: anti-radicals, enzyme inhibition, simulation and behavioral studies in animal models - Mahnashi_2023_J.Biomol.Struct.Dyn__1
Author(s) : Mahnashi MH , Ali S , O MA , Almazni IA , Asiri SA , Sadiq A , Zafar R , Jan MS
Ref : J Biomol Struct Dyn , :1 , 2023
Abstract : Alzheimer's disease (AD) is a neurological disorder that progresses gradually but irreversibly leading to dementia and is difficult to prevent and treat. There is a considerable time window in which the progression of the disease can be intervened. Scientific advances were required to help the researchers to identify the effective methods for the prevention and treatment of disease. This research was designed to investigate potential mediators for the remedy of AD, five new carboxylate amide zinc complexes (AAZ9-AAZ13) were synthesized and characterized by spectroscopic and physicochemical techniques. The biological evaluation was carried out based on the cholinesterase inhibitory mechanism. The preparation methodology provided the effective synthesis of targeted moieties. The in vitro pharmacological activities were evaluated involving AChE/BChE inhibition and antioxidant potential. All synthesized compounds displayed activity against both enzymes in higher or comparable to the standard drug Galantamine, a reversible inhibitor but the results displayed by compound AAZ10 indicated IC(50) of 0.0013 microM (AChE) and 0.061 microM (BChE) as high values for dual AChE/BChE inhibition with potent anti-oxidant results. Structure activity relationship (SAR) indicated that the potent activity of compound AAZ10 appeared due to the presence of nitro clusters at the ortho position of an aromatic ring. The potent synthesized compound AAZ10 was also explored for the in-vivo Anti-Alzheimer activity and anti-oxidant activity. Binding approaches of all synthesized compounds were revealed through molecular docking studies concerning binding pockets of enzymes that analyzed the best posture interaction with amino acid (AA) residues providing an appreciable understanding of enzyme inhibitory mechanisms. Results indicate that synthesized zinc (II) amide carboxylates can behave as an effective remedy in the treatment of Alzheimer's disease.Communicated by Ramaswamy H. Sarma.
ESTHER : Mahnashi_2023_J.Biomol.Struct.Dyn__1
PubMedSearch : Mahnashi_2023_J.Biomol.Struct.Dyn__1
PubMedID: 37642974

Title : Succinimide Derivatives as Antioxidant Anticholinesterases, Anti-alpha-Amylase, and Anti-alpha-Glucosidase: In Vitro and In Silico Approaches - Alshehri_2022_Evid.Based.Complement.Alternat.Med_2022_6726438
Author(s) : Alshehri OM , Mahnashi MH , Sadiq A , Zafar R , Jan MS , Ullah F , Alshehri MA , Alshamrani S , Hassan EE
Ref : Evid Based Complement Alternat Med , 2022 :6726438 , 2022
Abstract : Based on the diverse pharmacological potency and the structural features of succinimide, this research considered to synthesize succinimide derivatives. Moreover, these compounds were estimated for their biological potential in terms of anti-diabetic, anti-cholinesterase, and anti-oxidant capacities. The compounds were synthesized through Michael addition of various ketones to N-aryl maleimides. Similarly, the MOE software was used for the molecular docking study to explore the binding mode of the potent compounds against different enzymes. In the anti-cholinesterase activity, the compounds MSJ2 and MSJ10 exhibited outstanding activity against acetylcholinesterase (AChE), i.e., 91.90, 93.20%, and against butyrylcholinesterase (BChE), i.e., 97.30, 91.36% inhibitory potentials, respectively. The compounds MSJ9 and MSJ10 exhibited prominent alpha-glucosidase inhibitory potentials, i.e., 87.63 and 89.37 with IC(50) value of 32 and 28.04 microM, respectively. Moreover, the compounds MSJ2 and MSJ10 revealed significant scavenging activity against DPPH free radicals with IC(50) values of 2.59 and 2.52, while against ABTS displayed excellent scavenging potential with IC(50) values 7.32 and 3.29 microM, respectively. The tentative results are added with molecular docking studies in the active sites of enzymes to predict the theoretical protein-ligand binding modes. Further detailed mechanism-based studies in animal models are essential for the in vivo evaluation of the potent compound.
ESTHER : Alshehri_2022_Evid.Based.Complement.Alternat.Med_2022_6726438
PubMedSearch : Alshehri_2022_Evid.Based.Complement.Alternat.Med_2022_6726438
PubMedID: 35942378

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 : Diclofenac derivatives as concomitant inhibitors of cholinesterase, monoamine oxidase, cyclooxygenase-2 and 5-lipoxygenase for the treatment of Alzheimer's disease: synthesis, pharmacology, toxicity and docking studies - Javed_2022_RSC.Adv_12_22503
Author(s) : Javed MA , Bibi S , Jan MS , Ikram M , Zaidi A , Farooq U , Sadiq A , Rashid U
Ref : RSC Adv , 12 :22503 , 2022
Abstract : Targeting concomitantly cholinesterase (ChEs) and monoamine oxidases (MAO-A and MAO-B) is a key strategy to treat multifactorial Alzheimer's disease (AD). Moreover, it is reported that the expression of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) is increased significantly in the brain of AD patients. Using the triazole of diclofenac 12 as a lead compound, we synthesized a variety of analogs as multipotent inhibitors concomitantly targeting COX-2, 5-LOX, AChE, BChE, MAO-A and MAO-B. A number of compounds showed excellent in vitro inhibition of the target biological macromolecules in nanomolar concentration. Compound 39 emerged as the most potent multitarget ligand with IC(50) values of 0.03 microM, 0.91 microM, 0.61 microM, 0.01 microM 0.60 microM and 0.98 microM towards AChE, BChE, MAO-A, MAO-B, COX-2 and 5-LOX respectively. All the biologically active compounds were found to be non-neurotoxic and blood-brain barrier penetrant by using PAMPA assay. In a reversibility assay, all the studied active compounds showed reversibility and thus were found to be devoid of side effects. MTT assay results on neuroblastoma SH-SY5Y cells showed that the tested compounds were non-neurotoxic. An in vivo acute toxicity study showed the safety of the synthesized compounds up to a 2000 mg kg(-1) dose. In docking studies three-dimensional construction and interaction with key residues of all the studied biological macromolecules helped us to explain the experimental results.
ESTHER : Javed_2022_RSC.Adv_12_22503
PubMedSearch : Javed_2022_RSC.Adv_12_22503
PubMedID: 36105972

Title : In-Vitro, In-Vivo, Molecular Docking and ADMET Studies of 2-Substituted 3,7-Dihydroxy-4H-chromen-4-one for Oxidative Stress, Inflammation and Alzheimer's Disease - Mahnashi_2022_Metabolites_12_
Author(s) : Mahnashi MH , Alshahrani MA , Nahari MH , Hassan SSU , Jan MS , Ayaz M , Ullah F , Alshehri OM , Alshehri MA , Rashid U , Sadiq A
Ref : Metabolites , 12 : , 2022
Abstract : Plants' bioactives are well-known safe drugs for vital diseases. Flavones and Flavonoid-rich dietary supplements are known to exhibit neuroprotective potential. In this study, we isolated a flavone 2-(3,4-dimethoxyphenyl)-3,7-dihydroxy-4H-chromen-4-one from Notholirion thomsonianum and it was evaluated against various targets of the oxidative stress-related neurological disorders. The compound showed excellent acetyl and butyrylcholinesterase inhibitions in its profile, giving IC(50) values of 1.37 and 0.95 M, respectively. Similarly, in in-vitro MAO-B assay, our flavone exhibited an IC(50) value of 0.14 M in comparison to the standard safinamide (IC(50) 0.025 M). In in-vitro anti-inflammatory assay, our isolated compound exhibited IC(50) values of 7.09, 0.38 and 0.84 M against COX-1, COX-2 and 5-LOX, respectively. The COX-2 selectivity (SI) of the compound was 18.70. The compound was found safe in animals and was very effective in carrageenan-induced inflammation. Due to the polar groups in the structure, a very excellent antioxidant profile was observed in both in-vitro and in-vivo models. The compound was docked into the target proteins of the respective activities and the binding energies confirmed the potency of our compound. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) results showed that the isolated flavone has a good GIT absorption ability and comes with no hepatic and cardiotoxicity. In addition, the skin sensitization test, in-vitro human cell line activation test (h-CLAT) and KeratinoSens have revealed that isolated flavone is not skin sensitive with a confidence score of 59.6% and 91.6%. Herein, we have isolated a natural flavone with an effective profile against Alzheimer's, inflammation and oxidative stress. The exploration of this natural flavone will provide a baseline for future research in the field of drug development.
ESTHER : Mahnashi_2022_Metabolites_12_
PubMedSearch : Mahnashi_2022_Metabolites_12_
PubMedID: 36355138

Title : Neuroprotective potentials of selected natural edible oils using enzyme inhibitory, kinetic and simulation approaches - Mahnashi_2021_BMC.Complement.Med.Ther_21_248
Author(s) : Mahnashi MH , Alyami BA , Alqahtani YS , Alqarni AO , Jan MS , Ayaz M , Ullah F , Shahid M , Rashid U , Sadiq A
Ref : BMC Complement Med Ther , 21 :248 , 2021
Abstract : BACKGROUND: Edible oils have proven health benefits in the prevention and treatment of various disorders since the establishment of human era. This study was aimed to appraise neuropharmacological studies on the commonly used edible oils including Cinnamomum verum (CV), Zingiber officinale (ZO) and Cuminum cyminum (CC). METHODS: The oils were analyzed via GC-MS for identifications of bioactive compounds. Anti-radicals capacity of the oils were evaluated via 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals scavenging assays. The samples were also tested against two important acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which are among the important drug targets in Alzheimer's disease. Lineweaver-Burk plots were constructed for enzyme inhibition studies which correspond to velocity of enzymes (V(max)) against the reciprocal of substrate concentration (K(m)) in the presence of test samples and control drugs following Michaelis-Menten kinetics. Docking studies on AChE target were also carried out using Molecular Operating Environment (MOE 2016.0802) software. RESULTS: (Gas chromatography-mass spectrometry GC-MS) analysis revealed the presence of thirty-four compounds in Cinnamon oil (Cv.Eo), fourteen in ginger oil (Zo.Eo) and fifty-six in cumin oil (Cc.Eo). In the antioxidant assays, Cv.Eo, Zo.Eo and Cc.Eo exhibited IC(50) values of 85, 121, 280 microg/ml sequentially against DPPH radicals. Whereas, in ABTS assay, Cv.Eo, Zo.Eo and Cc.Eo showed considerable anti-radicals potentials with IC(50) values of 93, 77 and 271 microg/ml respectively. Furthermore, Cv.Eo was highly active against AChE enzyme with IC(50) of 21 microg/ml. Zo.Eo and Cc.Eo exhibited considerable inhibitory activities against AChE with IC(50) values of 88 and 198 microg/ml respectively. In BChE assay, Cv.Eo, Zo.Eo and Cc.Eo exhibited IC(50) values of 106, 101 and 37 microg/ml respectively. Our results revealed that these oils possess considerable antioxidant and cholinesterase inhibitory potentials. As functional foods these oils can be effective remedy for the prevention and management of neurological disorders including AD. Synergistic effect of all the identified compounds was determined via binding energy values computed through docking simulations. Binding orientations showed that all the compounds interact with amino acid residues present in the peripheral anionic site (PAS) and catalytic anionic site (CAS) amino acid residues, oxyanion hole and acyl pocket via Pi-Pi stacking interactions and hydrogen bond interactions.
ESTHER : Mahnashi_2021_BMC.Complement.Med.Ther_21_248
PubMedSearch : Mahnashi_2021_BMC.Complement.Med.Ther_21_248
PubMedID: 34600509

Title : Pharmacological Evaluation of Aldehydic-Pyrrolidinedione Against HCT-116, MDA-MB231, NIH\/3T3, MCF-7 Cancer Cell Lines, Antioxidant and Enzyme Inhibition Studies - Ahmad_2019_Drug.Des.Devel.Ther_13_4185
Author(s) : Ahmad A , Ullah F , Sadiq A , Ayaz M , Rahim H , Rashid U , Ahmad S , Jan MS , Ullah R , Shahat AA , Mahmood HM
Ref : Drug Des Devel Ther , 13 :4185 , 2019
Abstract : Purpose: The current work was designed to synthesize a bioactive derivative of succinimide and evaluate it for anti-Alzheimer, anticancer and anti-diabetic potentials. Methods: The compound was synthesized by Michael addition of butyraldehyde with N-phenylmaleimide. The synthesized compound was screened for biological potentials including anti-cholinesterase, in-vitro anti-diabetic, antioxidant and anthelmintic potentials. The anti-cholinesterase potential was evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), anti-diabetic potential against alpha-glucosidase, antioxidant potential against ABTS, DPPH and H2O2 and anthelmintic potential against Perethima posthuma and Ascaridia galli respectively. Results: The compound demonstrated significant AChE and BChE inhibition i.e., 71.34+/-1.92 and 73.42 +/-1.92 at the concentration of 1000 microg/mL respectively. Other dilutions exhibited concentration-dependent inhibitory activity against both enzymes. In the MTT assay, the newly synthesized compound was found active against all of the cell lines viz, HCT-116, MDA-MB231, NIH/3T3 and MCF-7 and the highest cytotoxicity potential was observed against the colon cancer cell line (HCT-116) with an IC50 value of 78 microg/mL exhibiting its highest potential. Moreover, the compound exhibited prominent alpha-glucosidase inhibitory potentials (79.86+/-2.54% at 1000 microg/mL) with IC50 value of 156.23 microg/mL. Further, our test compound exhibited considerable scavenging activity against DPPH, ABTS and H2O2 free radicals with percent inhibitions of 75.84+/-1.58, 72.85+/-1.17 and 54.82+/-1.82 and IC50 values of 84.36, 139.74 and 752.21 microg/mL respectively. Our test sample exhibited significant anthelmintic potentials. It demonstrated significant paralysis and death of the test worms in an unbelievably short time in comparison with albendazole. Conclusion: Going into the detail of all observations, it may be deduced that the newly synthesized succinimide derivative could be an important drug candidate against neurodegenerative disorders like Alzheimer's disease, cancer, diabetes mellitus and worms. Further detailed studies in animal models are required for in-vivo analysis of the compound.
ESTHER : Ahmad_2019_Drug.Des.Devel.Ther_13_4185
PubMedSearch : Ahmad_2019_Drug.Des.Devel.Ther_13_4185
PubMedID: 31849450

Title : HPLC-DAD finger printing, antioxidant, cholinesterase, and alpha-glucosidase inhibitory potentials of a novel plant Olax nana - Ovais_2018_BMC.Complement.Altern.Med_18_1
Author(s) : Ovais M , Ayaz M , Khalil AT , Shah SA , Jan MS , Raza A , Shahid M , Shinwari ZK
Ref : BMC Complement Altern Med , 18 :1 , 2018
Abstract : BACKGROUND: The medicinal importance of a novel plant Olax nana Wall. ex Benth. (family: Olacaceae) was revealed for the first time via HPLC-DAD finger printing, qualitative phytochemical analysis, antioxidant, cholinesterase, and alpha-glucosidase inhibitory assays. METHODS: The crude methanolic extract of O. nana (ON-Cr) was subjected to qualitative phytochemical analysis and HPLC-DAD finger printing. The antioxidant potential of ON-Cr was assessed via 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS) and hydrogen peroxide (H2O2) free radical scavenging assays. Furthermore, acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities were performed using Ellman's assay, while alpha- glucosidase inhibitory assay was carried out using a standard protocol. RESULTS: The qualitative phytochemical analysis of ON-Cr revealed the presence of secondary metabolites like alkaloids, flavonoids, tannins, sterols, saponins and terpenoids. The HPLC-DAD finger printing revealed the presence of 40 potential compounds in ON-Cr. Considerable anti-radical activities was revealed by ON-Cr in the DPPH, ABTS and H2O2 free radical scavenging assays with IC50 values of 71.46, 72.55 and 92.33 mug/mL, respectively. Furthermore, ON-Cr showed potent AChE and BChE inhibitory potentials as indicated by their IC50 values of 33.2 and 55.36 mug/mL, respectively. In the alpha-glucosidase inhibition assay, ON-Cr exhibited moderate inhibitory propensity with an IC50 value of 639.89 mug/mL. CONCLUSIONS: This study investigated Olax nana for the first time for detailed qualitative phytochemical tests, HPLC-DAD finger printing analysis, antioxidant, anticholinesterase and alpha-glucosidase inhibition assays. The antioxidant and cholinesterase inhibitory results were considerable and can provide scientific basis for further studies on the neuroprotective and anti-Alzheimer's potentials of this plant. ON-Cr may further be subjected to fractionation and polarity guided fractionation to narrow down the search for isolation of bioactive compounds.
ESTHER : Ovais_2018_BMC.Complement.Altern.Med_18_1
PubMedSearch : Ovais_2018_BMC.Complement.Altern.Med_18_1
PubMedID: 29295712

Title : Design, synthesis and bioevaluation of tricyclic fused ring system as dual binding site acetylcholinesterase inhibitors - Tanoli_2018_Bioorg.Chem_83_336
Author(s) : Tanoli ST , Ramzan M , Hassan A , Sadiq A , Jan MS , Khan FA , Ullah F , Ahmad H , Bibi M , Mahmood T , Rashid U
Ref : Bioorg Chem , 83 :336 , 2018
Abstract : Due to recently discovered non-classical acetylcholinesterase (AChE) function, dual binding-site AChE inhibitors have acquired a paramount attention of drug designing researchers. The unique structural arrangements of AChE peripheral anionic site (PAS) and catalytic site (CAS) joined by a narrow gorge, prompted us to design the inhibitors that can interact with dual binding sites of AChE. Eighteen homo- and heterodimers of desloratadine and carbazole (already available tricyclic building blocks) were synthesized and tested for their inhibition potential against electric eel acetylcholinesterase (eeAChE) and equine serum butyrylcholinesterase (eqBChE). We identified a six-carbon tether heterodimer of desloratadine and indanedione based tricyclic dihydropyrimidine (4c) as potent and selective inhibitor of eeAChE with IC50 value of 0.09+/-0.003muM and 1.04+/-0.08muM (for eqBChE) with selectivity index of 11.1. Binding pose analysis of potent inhibitors suggest that tricyclic ring is well accommodated into the AChE active site through hydrophobic interactions with Trp84 and Trp279. The indanone ring of most active heterodimer 4b is stabilized into the bottom of the gorge and forms hydrogen bonding interactions with the important catalytic triad residue Ser200.
ESTHER : Tanoli_2018_Bioorg.Chem_83_336
PubMedSearch : Tanoli_2018_Bioorg.Chem_83_336
PubMedID: 30399465

Title : Anticholinesterase and antioxidant potentials of Nonea micrantha Bioss. & Reut along with GC-MS analysis - Imran_2017_BMC.Complement.Altern.Med_17_499
Author(s) : Imran M , Ullah F , Ayaz M , Sadiq A , Shah MR , Jan MS
Ref : BMC Complement Altern Med , 17 :499 , 2017
Abstract : BACKGROUND: Nonea micrantha Boiss. & Reut . being an unexplored member of Boraginaceae was investigated for GC/MS analysis, acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory and antioxidant activities in an attempt to find its effectiveness in neurological disorders.
METHODS: The AChE and BChE inhibitory activities of crude methanolic extract (Nm.Cr), subsequent fractions; n-hexane (Nm.Hex), chloroform (Nm.Cf), ethyl acetate (Nm.EtAc), aqueous (Nm.Aq) and crude saponins (Nm.Sp) from N. micrantha were conducted using Ellman's assay. The antioxidant activity of the plant samples using DPPH and ABTS free radical scavenging potential following quantitative spectrophotometric and qualitative TLC method were also studied. Moreover the total reducing power (TRP) of all the samples was also figured out.
RESULTS: The GC/Ms analysis confirmed that the plant is rich in bioactive molecules. Among different fractions, Nm.Hex, Nm.EtAc and Nm.Cf exhibited highest AChE inhibitory activities causing 75.51 +/- 0.73, 68.54 +/- 0.59 and 63.48 +/- 0.59% enzyme inhibition respectively and IC50 of 44, 100 and 144 mug/mL respectively. In BChE inhibiton assay, Nm.Aq, Nm.Sp and Nm.Cr showed highest activity causing 83.49 +/- 0.27, 81.49 +/- 0.89 and 75.31 +/- 0.56% enzyme inhibition with IC50 of 90, 110 and 44 mug/mL respectively. In DPPH assay, Nm.Aq, Nm.Cf, Nm.Hex and Nm.Cr were most potent exhibiting IC50 values of 3, 5, 93 and 120 mug/ml respectively. In ABTS assay Nm.EtAc, Nm.Aq, Nm.Sp and Nm.Cr showed IC50 values of 60, 95, 100 and 150 mug/mL respectively. Likewise ABTS inhibition was most prominent for Nm.Sp, Nm.EtAc and Nm.Aq causing 78.26 +/- 0.49, 67.67 +/- 0.73 and 63.58 +/- 0.45% inhibition respectively at 1 mg/mL. These results were further confirmed by qualitative screening using DPPH and ABTS staining.
CONCLUSIONS: Our anticholinesterase and antioxidant results signify the N. micrantha as a potential source of natural bioactive compounds. Moreover isolation of natural bioactive compounds from this plant may lead to novel drug candidates against neurodegenerative disorders.
ESTHER : Imran_2017_BMC.Complement.Altern.Med_17_499
PubMedSearch : Imran_2017_BMC.Complement.Altern.Med_17_499
PubMedID: 29169349

Title : Synthesis, anticholinesterase and antioxidant potentials of ketoesters derivatives of succinimides: a possible role in the management of Alzheimer's - Sadiq_2015_Chem.Cent.J_9_31
Author(s) : Sadiq A , Mahmood F , Ullah F , Ayaz M , Ahmad S , Haq FU , Khan G , Jan MS
Ref : Chem Cent J , 9 :31 , 2015
Abstract : BACKGROUND: Based on the pharmacological potency and structural features of succinimides, this study was designed to synthesize new ketoesters derivatives of succinimides. Furthermore, the synthesized compounds were evaluated for their possible anticholinesterase and antioxidant potentials. The compounds were synthesized by organocatalytic Michael additions of alpha-ketoesters to N-aryl maleimides. Acetyl and butyrylcholinesterase inhibitory activities were determined using Ellman's spectrophotometric assay. The antioxidant activity was performed with DPPH and ABTS free radicals scavenging assay.
RESULTS: The Michael additions of alpha-ketoesters to maleimides was promoted by 8-hydroxyquinoline. The organocatalyst (8-hydroxyquinoline, 20 mol %) produced the compounds in relatively shorter time (20-24 h) and with excellent isolated yields (84-98 %). The synthesized compounds (1-4) showed outstanding acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potentials, i.e., 98.75 and 90.00 % respectively for compound 2, with IC50 < 0.1 mug/mL. Additionally, compounds 1-4 revealed moderate antioxidant activity at different concentrations. In DPPH free radical scavenging assay, compound 1 showed dominant result with 72.41 +/- 0.45, 52.49 +/- 0.78 and 35.60 +/- 0.75 % inhibition at concentrations of 1000, 500 and 250 mug/mL respectively, IC50 value of 440 mug/mL. However, the free radical scavenging was better when used ABTS free radicals. In ABTS free radicals scavenging assay compound 1 exhibited 88.51 +/- 0.62 % inhibition at highest tested concentration i.e., 1000 mug/mL.
CONCLUSIONS: Herein, we have synthesized four ketoesters derivatives of succinimides in a single step reaction and high yields. As a highlight, we have showed a first report on the anticholinesterase and antioxidant potentials of succinimides. All the compounds showed overwhelming enzyme inhibitions and moderate antioxidant potentials. Graphical AbstractGraphical representation of synthesis, anticholinesterase and antioxidant potentials of ketoester derivatives of succinimides.
ESTHER : Sadiq_2015_Chem.Cent.J_9_31
PubMedSearch : Sadiq_2015_Chem.Cent.J_9_31
PubMedID: 26064188