Ullah R

References (14)

Title : Vanillin derivatives as antiamnesic agents in scopolamine-induced memory impairment in mice - Gul_2024_Heliyon_10_e26657
Author(s) : Gul Q , Karim N , Shoaib M , Zahoor M , Rahman MU , Bilal H , Ullah R , Alotaibi A
Ref : Heliyon , 10 :e26657 , 2024
Abstract : Amnesia is a major health problem prevalent in almost every part of the world specifically in old age peoples. Vanillin analogues have played an important role in the field medicines. Some of them have been documented to be promising inhibitors of cholinesterases and could therefore, be used as antidepressant, anti-Alzheimer and as neuroprotective drugs. In this connection, the present study was designed to synthesize new vanillin analogues (SB-1 to SB-6) of varied biological potentials. The synthesized compounds were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and as scavengers of DPPH and ABTS free radicals followed by behavioural antiamnesic evaluation in mice. The compounds; SB-1, SB-3, SB-4 and SB-6 more potently inhibited AChE with IC(50) values of 0.078, 0.157, 0.108, and 0.014 microM respectively. The BChE was more potently inhibited by SB-3 with IC(50) of 0.057 microM. Moreover, all of the tested compounds exhibited strong antioxidant potentials with promising results of SB-3 against DPPH with IC(50) of 0.305 microM, while SB-5 was most active against ABTS with IC(50) of 0.190 microM. The in-vivo studies revealed the improvement in memory deficit caused by scopolamine. Y-Maze and new object recognition test showed a considerable decline in cognitive dysfunctions. In Y-Maze test the spontaneous alteration of 69.44 +/- 1% and 84.88 +/- 1.35% for SB-1 and 68.92 +/- 1% and 80.89 +/- 1% for SB-3 at both test doses were recorded while during the novel object recognition test the Discrimination Index percentage of SB-1 was more pronounced as compared to standard drug. All compounds were found to be potent inhibitors of AChE, BChE, DPPH, and ABTS in vitro however, SB-1 and SB-3 were comparatively more potent. SB-1 was also more active in reclamation of memory deficit caused by scopolamine. SB-1 and SB-3 may be considered as excellent drug candidates for treating amnesia subjected to toxicological evaluations in other animal models.
ESTHER : Gul_2024_Heliyon_10_e26657
PubMedSearch : Gul_2024_Heliyon_10_e26657
PubMedID: 38420420

Title : Development of Iron Nanoparticles (FeNPs) Using Biomass of Enterobacter: Its Characterization, Antimicrobial, Anti-Alzheimer's, and Enzyme Inhibition Potential - Zafar_2022_Micromachines.(Basel)_13_
Author(s) : Zafar S , Faisal S , Jan H , Ullah R , Rizwan M , Abdullah , Alotaibi A , Bibi N , Rashid AU , Khattak A
Ref : Micromachines (Basel) , 13 : , 2022
Abstract : Nanotechnology is a new field that has gained considerable importance due to its potential uses in the field of biosciences, medicine, engineering, etc. In the present study, bio-inspired metallic iron nanoparticles (FeNPs) were prepared using biomass of Enterobacter train G52. The prepared particles were characterized by UV-spectroscopy, TGA, XRD, SEM, EDX, and FTIR techniques. The crystalline nature of the prepared FeNPs was confirmed by XRD. The SEM techniques revealed the particles size to be 23 nm, whereas in FTIR spectra the peaks in the functional group region indicated the involvement of bioactive compounds of selected bacterial strains in the capping of FeNPs. The EDX confirmed the presence of iron in the engineered FeNPs. The FeNPs were then evaluated for its antibacterial, antifungal, antioxidant, anti-inflammatory, anti-Alzheimer's, anti-larvicidal, protein kinase inhibition, anti-diabetic, and biocompatibility potentials using standard protocols. Substantial activities were observed in almost all biological assays used. The antioxidant, anti-cholinesterase, and anti-diabetic potential of the prepared nanoparticles were high in comparison to other areas of biological potential, indicating that the FeNPs are capable of targeting meditators of oxidative stress leading to diabetes and Alzheimer's disease. However, the claim made needs some further experimentation to confirm the observed potential in in vivo animal models.
ESTHER : Zafar_2022_Micromachines.(Basel)_13_
PubMedSearch : Zafar_2022_Micromachines.(Basel)_13_
PubMedID: 36014181

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 : Phytochemical Analysis, In Vitro Anticholinesterase, Antioxidant Activity and In Vivo Nootropic Effect of Ferula ammoniacum (Dorema ammoniacum) D. Don. in Scopolamine-Induced Memory Impairment in Mice - Nazir_2021_Brain.Sci_11_
Author(s) : Nazir N , Nisar M , Zahoor M , Uddin F , Ullah S , Ullah R , Ansari SA , Mahmood HM , Bari A , Alobaid A
Ref : Brain Sci , 11 : , 2021
Abstract : BACKGROUND: Ferula ammoniacum (D. Don) is one of the endemic medicinal plants that is traditionally used to treat a number of diseases. Although the plant has been used to enhance memory, the investigational evidence supporting the nootropic effect was unsubstantial. Hence, the rationale for this study was to assess the potential beneficial effect of F. ammoniacum seed extracts on learning and memory in mice. METHODS: The powdered plant samples (aerial parts) were subjected to extraction ad fractionation. Among the extracts, crude and ethyl acetate extracts were screened for major phytochemicals through HPLC analysis. All the extracts were evaluated for the in vitro anticholinesterase (AChE and BChE) and antioxidant potentials. Among the extracts the active fraction was further assessed for improving learning and memory in mice using behavioural tests like Y-maze and novel object recognition test (NORT) using standard protocols. After behavioural tests, all the animals were sacrificed and brains tissues were assessed for the ex vivo anticholinesterase and antioxidant potentials. RESULTS: Phytochemicals like chlorogenic acid, quercetin, mandelic acid, phloroglucinol, hydroxy benzoic acid, malic acid, epigallocatechin gallate, ellagic acid, rutin, and pyrogallol were identified in crude methanolic extract (Fa.Met) and ethyl acetate fraction (Fa.EtAc) through HPLC. Fa.EtAc and Fa.Chf extracts more potently inhibited AChE and BChE with IC50 values of 40 and 43 microg/mL, and 41 and 42 microg/mL, respectively. Similarly highest free radical scavenging potential was exhibited by Fa.EtAc fraction against DPPH (IC50 = 100 microg/mL) and ABTS (IC50 = 120 microg/mL). The extract doses, 100 and 200 mg/kg body weight significantly (p < 0.01) improved the short-term memory by increasing the percent spontaneous alternation in the Y-maze test along with increasing discrimination index in the NORT that clearly indicated the enhancement in the recognition memory of mice. CONCLUSION: The extracts more potently scavenged the tested free radicals, exhibited anticholinesterase activities, improved the learning abilities and reduced the memory impairment induced by scopolamine in mice model thus suggesting that these extracts could be effectively used for the management of oxidative stress, neurodegenerative diseases and memory loss.
ESTHER : Nazir_2021_Brain.Sci_11_
PubMedSearch : Nazir_2021_Brain.Sci_11_
PubMedID: 33669503

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 : Behavioral and Biochemical Effects of Mukia madrespatana Following Single Immobilization Stress on Rats - Samad_2020_Medicina.(Kaunas)_56_
Author(s) : Samad N , Ali A , Yasmin F , Ullah R , Bari A
Ref : Medicina (Kaunas) , 56 : , 2020
Abstract : Elevated oxidative stress has been shown to play an important role in the diagnosis and prognosis of stress and memory-related complications. Mukia madrespatana (M. madrespatana) has been reported to have various biological and antioxidant properties. We intended to evaluate the effect of M. madrespatana peel on single immobilization stress-induced behavioral deficits and memory changes in rats. Materials and Methods: M. madrespatana peel (2000 mg/kg/day, orally) was administered to control and immobilize stressed animals for 4 weeks. Anxiolytic, antidepressant, and memory-enhancing effects of M. madrespatana were observed in both unstressed and stressed animals. Results: Lipid peroxidation was decreased while antioxidant enzymes were increased in both unstressed and stressed animals. Acetylcholine level was increased while acetylcholinesterase activity was decreased in both M. madrespatana treated unstressed and stressed rats. There was also an improvement in memory function. Serotonin neurotransmission was also regulated in M. madrespatana treated rats following immobilization stress with anxiolytic and anti-depressive effects. Conclusion: Based on the current study, it is suggested that M. madrespatana has strong antioxidant properties and may be beneficial as dietary supplementation in stress and memory-related conditions.
ESTHER : Samad_2020_Medicina.(Kaunas)_56_
PubMedSearch : Samad_2020_Medicina.(Kaunas)_56_
PubMedID: 32674473

Title : Synthetic beta-hydroxy ketone derivative inhibits cholinesterases, rescues oxidative stress and ameliorates cognitive deficits in 5XFAD mice model of AD - Ahmad_2020_Mol.Biol.Rep_47_9553
Author(s) : Ahmad SI , Ali G , Muhammad T , Ullah R , Umar MN , Hashmi AN
Ref : Mol Biol Rep , 47 :9553 , 2020
Abstract : Alzheimer's disease (AD) is a progressive, chronic and age-related neurodegenerative disorder that affects millions of people across the world. In pursuit of new anti-AD remedies, 2-[Hydroxy-(4-nitrophenyl)methyl]-cyclopentanone (NMC), a beta hydroxyl ketone derivative was studied to explore its neuroprotective potentials against AD. The in-vitro AChE and BuChE enzymes inhibition were evaluated by Ellman protocol and antioxidant potentials of NMC by DPPH free radical scavenging assay. In-vivo behavioral studies were performed in the transgenic 5xFAD mice model of AD using shallow water maze (SWM), Paddling Y-Maze (PYM), elevated plus maze (EPM) and balance beam (BB) tests. Also, the ex-vivo cholinesterase inhibitory effects of NMC and histopathological analysis of amyloid-beta plaques were determined in the frontal cortex and hippocampal regions of the mice brain. NMC exhibited significant in vitro anti-cholinesterase enzyme potentials with an IC(50) value of 67 microg/ml against AChE and 96 microg/ml against BuChE respectively. Interestingly, the activities of AChE and BuChE enzymes were also significantly lower in the cortex and hippocampus of NMC-treated groups. Also, in the DPPH assessment, NMC displayed substantial antioxidant properties with an IC(50) value observed as 171 microg/ml. Moreover, histopathological analysis via thioflavin-s staining displayed significantly lower plaques depositions in the cortex and hippocampus region of NMC-treated mice groups. Furthermore, SWM, PYM, EPM, and BB behavioral analysis indicated that NMC enhanced spatial learning, memory consolidation and improved balance performance. Altogether, to the best of our knowledge, we believe that NMC may serve as a potential and promising anti-cholinesterase, antioxidant and neuroprotective agent against AD.
ESTHER : Ahmad_2020_Mol.Biol.Rep_47_9553
PubMedSearch : Ahmad_2020_Mol.Biol.Rep_47_9553
PubMedID: 33211296

Title : Evaluation of Cholinesterase Inhibitory Potential of Different Genotypes of Ziziphus nummularia, Their HPLC-UV, and Molecular Docking Analysis - Uddin_2020_Molecules_25_5011
Author(s) : Uddin N , Ali N , Uddin Z , Nazir N , Zahoor M , Rashid U , Ullah R , Alqahtani AS , Alqahtani AM , Nasr FA , Liu M , Nisar M
Ref : Molecules , 25 :5011 , 2020
Abstract : Ziziphus nummularia is an important source of valuable phytoconstituents, which are widely used in traditional medicine system of Indo-Pak sub-continent. In this study we investigated the distribution of phenolic compounds in the fruit pericarps of six different genotypes (ZNP01-06) of Z. nummularia growing in the unexplored hilly areas of Pakistan. The methanolic extracts of these genotypes were screened for total phenolic content (TPC), total flavonoid content (TFC), antioxidant, and cholinesterase inhibitory potentials. The observed biological potentials were explained in terms of the outcome of molecular docking and HPLC analyses. Among them, genotype ZNP02 displayed high TPC (88.50 +/- 1.23 g/mL) and showed potent scavenging activity against DPPH (67.03 +/- 1.04 g/mL) and ABTS (65.3 +/- 1.74 g/mL) in comparison to ascorbic acid (68.7 +/- 0.47 g/mL). Moreover, genotypes ZNP01, ZNP02, and ZNP04 displayed potent inhibition against acetyl and butyryl cholinesterases (AChE and BChE) with IC(50) values of 21.2, 20.5, and 23.7 g/mL (AChE) and 22.7, 24.4, and 33.1 g/mL (BChE), respectively. Furthermore, the individual compounds in the most potent species ZNP01 responsible for potent enzyme inhibition (identified through HPLC-UV analysis), were computed via docking simulation software to the enzyme structures. Among these compounds rutin exhibited significant binding affinity with value of -9.20 kcal/mol. The differences amongst the phytochemical compositions of the selected genotypes highlighted the genotypic variations in them. Based on our results it was concluded that the selected plant can be used as remedy of oxidative stress and neurodegenerative diseases. However, further studies are needed to isolate responsible compounds and test the observed potential in vivo, along with toxicological evaluations in animal models.
ESTHER : Uddin_2020_Molecules_25_5011
PubMedSearch : Uddin_2020_Molecules_25_5011
PubMedID: 33137939

Title : Comparative Cholinesterase, alpha-Glucosidase Inhibitory, Antioxidant, Molecular Docking, and Kinetic Studies on Potent Succinimide Derivatives - Ahmad_2020_Drug.Des.Devel.Ther_14_2165
Author(s) : Ahmad A , Ullah F , Sadiq A , Ayaz M , Saeed Jan M , Shahid M , Wadood A , Mahmood F , Rashid U , Ullah R , Sahibzada MUK , Alqahtani AS , Mahmood HM
Ref : Drug Des Devel Ther , 14 :2165 , 2020
Abstract : Introduction: The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays. Methods: In this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and alpha-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver-Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis-Menten kinetics. Results: In AChE inhibitory assay, compounds 1 and 2 exhibited IC50 of 343.45 and 422.98 microM, respectively, against AChE enzyme. Similarly, both the compounds showed IC50 of 276.86 and 357.91 microM, respectively, against BChE enzyme. Compounds 1 and 2 displayed IC50 of 157.71 and 471.79 microM against alpha-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC50 values of 297.98, 332.94, and 825.92 microM against DPPH, ABTS, and H2O2 free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2. The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound 2. Conclusion: Both succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and alpha-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties.
ESTHER : Ahmad_2020_Drug.Des.Devel.Ther_14_2165
PubMedSearch : Ahmad_2020_Drug.Des.Devel.Ther_14_2165
PubMedID: 32606589

Title : Attenuation of Spatial Memory in 5xFAD Mice by Halting Cholinesterases, Oxidative Stress and Neuroinflammation Using a Cyclopentanone Derivative - Ullah_2020_Pharmaceuticals.(Basel)_13_
Author(s) : Ullah R , Ali G , Ahmad N , Akram M , Kumari G , Amin MU , Umar MN
Ref : Pharmaceuticals (Basel) , 13 : , 2020
Abstract : Alzheimer's disease (AD) is an irreversible and chronic neurological disorder that gradually destroys memory and thinking skills. The research study was designed to investigate the underlying molecular signaling involved in the neuroprotective effects of cyclopentanone derivative i.e., 2-(hydroxyl-(3-nitrophenyl)methyl)cyclopentanone (3NCP) as a therapeutic agent for AD. In this study, In vivo studies were carried out on a well-known 5xFAD mice model using different behavioural test models such as open field, rotarod, Morris water maze (MWM), and Y-maze tests. Furthermore, in vitro cholinesterase inhibition activity assays were carried out. The frontal cortex (FC) and hippocampus (HC) homogenates were tested for the levels/activities of cholinesterases, glutathione (GSH), glutathione S-transferase (GST), and catalase. Furthermore, the hippocampal expression of inflammatory cytokines was observed via RT-PCR and western blot. The results of in vivo studies show an enhancement in the learning behavior. The 3NCP treatment reduced latency time in MWM and Y-maze tests, also increase spontaneous alternation indicate significant effect of 3NCP on memory. Furthermore, open field and rotarod studies revealed that 3NCP does not cause motor coordination deficit. The results of the in vitro studies revealed that the IC(50) values of the 3NCP against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were 16.17 and 20.51 microg/mL, respectively. This decline in AChE and BChE was further supported by ex vivo studies. Further, the 3NCP mitigates the GSH level, GST, and catalase activities in HC and FC. The mRNA and protein expression of inflammatory cytokines (IL-1beta, IL-6, TNF-alpha) markedly declined in RT-PCR and western blotting. The results of the current study conclusively demonstrate that 3NCP reduces oxidative stress and mitigates neuroinflammation in 5xFAD mice, implying that 3NCP may be a potential therapeutic candidate for AD treatment in the future.
ESTHER : Ullah_2020_Pharmaceuticals.(Basel)_13_
PubMedSearch : Ullah_2020_Pharmaceuticals.(Basel)_13_
PubMedID: 33086500

Title : 4-Benzyloxylonchocarpin and Muracatanes A-C from Ranunculus muricatus L. and Their Biological Effects - Hussain_2020_Biomolecules_10_
Author(s) : Hussain H , Ali I , Wang D , Mamadalieva NZ , Hussain W , Csuk R , Loesche A , Fischer L , Staerk D , Anam S , AlZain MN , Mushtaq M , Ul-Haq Z , Ullah R , Noman OM , Abbas G , Green IR
Ref : Biomolecules , 10 : , 2020
Abstract : Ranunculus muricatus L. is a spiny fruit buttercup that is used in various traditional medicinal systems. In the current investigation of R. muricatus, the new chalcone 4-benzyloxylonchocarpin (1), the new anthraquinone muracatanes A (2), the new-to-nature anthraquinone muracatanes B (3), and the new naphthalene analog muracatanes C (4) were isolated, in addition to the three previously reported compounds, 4-methoxylonchocarpin (5), beta-sitosterol (6), and beta-sitosterol beta-D-glucopyranoside (7). Their structures were elucidated using 1D ((1)H and (13)C) and 2D (COSY, HSQC, and HMBC) NMR spectroscopy and HR-ESI-MS. Chalcone 1 showed potent acetylcholinesterase inhibitory effects with K(i) of 5.39 microM and K(i') of 3.54 microM, but none of the isolated compounds showed inhibitory activity towards butyrylcholinesterase. Anthraquinone 3 illustrated alpha-glucosidase inhibitory effects with IC(50)-values of 164.46 +/- 83.04 microM. Compound 5 displayed moderate cytotoxic activity towards ovarian carcinoma (A2780, IC(50) = 25.4 microM), colorectal adenocarcinoma (HT29, IC(50) = 20.2 microM), breast cancer (MCF7, IC(50) = 23.7 microM), and thyroid carcinoma (SW1736, IC(50) = 26.2 microM) while it was inactive towards pharynx carcinoma (FaDu: IC(50) > 30 microM).
ESTHER : Hussain_2020_Biomolecules_10_
PubMedSearch : Hussain_2020_Biomolecules_10_
PubMedID: 33212893

Title : Enzyme Inhibitory, Antioxidant And Antibacterial Potentials Of Synthetic Symmetrical And Unsymmetrical Thioureas - Naz_2019_Drug.Des.Devel.Ther_13_3485
Author(s) : Naz S , Zahoor M , Umar MN , Ali B , Ullah R , Shahat AA , Mahmood HM , Sahibzada MUK
Ref : Drug Des Devel Ther , 13 :3485 , 2019
Abstract : Background: In this study, 2 symmetrical and 3 unsymmetrical thioureas were synthesized to evaluate their antioxidant, antibacterial, antidiabetic, and anticholinesterase potentials. Methods: The symmetrical thioureas were synthesized in aqueous media in the presence of sunlight, using amines and CS2 as starting material. The unsymmetrical thioureas were synthesized using amines as a nucleophile to attack the phenyl isothiocyanate (electrophile). The structures of synthesized compounds were confirmed through H(1) NMR. The antioxidant potential was determined using DPPH and ABTS assays. The inhibition of glucose-6-phosphatase, alpha amylase, and alpha glucosidase by synthesized compounds was used as an indication of antidiabetic potential. Anticholinesterase potential was determined from the inhibition of acetylcholinesterase and butyrylcholinesterase by the synthesized compounds. Results: The highest inhibition of glucose-6-phosphatase was shown by compound V (03.12 mg of phosphate released). Alpha amylase was most potently inhibited by compound IV with IC50 value of 62 microg/mL while alpha glucosidase by compound III with IC50 value of 75 microg/mL. The enzymes, acetylcholinesterase, and butyrylcholinesterase were potently inhibited by compound III with IC50 of 63 microg/mL and 80 microg/mL respectively. Against DPPH free radical, compound IV was more potent (IC50 = 64 microg/mL) while ABTS was more potently scavenged by compound I with IC50 of 66 microg/mL. The antibacterial spectrum of synthesized compounds was determined against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Agrobacterium tumefaction and Proteus vulgaris). Compound I and compound II showed maximum activity against A. tumefaction with MIC values of 4.02 and 4.04 microg/mL respectively. Against P. vulgaris, compound V was more active (MIC = 8.94 microg/mL) while against S. aureus, compound IV was more potent with MIC of 4.03 microg/mL. Conclusion: From the results, it was concluded that these compounds could be used as antibacterial, antioxidant, and antidiabetic agents. However, further in vivo studies are needed to determine the toxicological effect of these compounds in living bodies. The compounds also have potential to treat neurodegenerative diseases.
ESTHER : Naz_2019_Drug.Des.Devel.Ther_13_3485
PubMedSearch : Naz_2019_Drug.Des.Devel.Ther_13_3485
PubMedID: 31631973

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 : Isolation, pharmacological evaluation and molecular docking studies of bioactive compounds from Grewia optiva - Ul Bari_2019_Drug.Des.Devel.Ther_13_3029
Author(s) : Ul Bari W , Zahoor M , Zeb A , Sahibzada MUK , Ullah R , Shahat AA , Mahmood HM , Khan I
Ref : Drug Des Devel Ther , 13 :3029 , 2019
Abstract : Background: Traditionally, Grewia optiva is widely used for the treatment of many diseases like dysentery, fever, typhoid, diarrhea, eczema, smallpox, malaria and cough. Methods: Shade-dried roots of G. optiva were extracted with methanol. Based on HPLC results, chloroform and ethyl acetate fractions were subjected to silica column isolation and four compounds: glutaric acid (V), 3,5 dihydroxy phenyl acrylic acid (VI), (2,5 dihydroxy phenyl) 3',6',8'-trihydroxyl-4H chromen-4'-one (VII) and hexanedioic acid (VIII) were isolated in pure form. Ellman's assay was used to determine the anticholinesterase potential of isolated compounds while their antioxidant potential was estimated by DPPH and ABTS scavenging assays. Results: Amongst the isolated compounds, VI and VII exhibited excellent percent inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (83.23+/-1.11, 82.72+/-2.20 and 82.11+/-2.11, 82.23+/-1.21, respectively, at 1000 microg/mL) with IC50 of 76, 90, 78 and 92 microg/mL, respectively. Highest percent radicals scavenging against DPPH and ABTS (87.41+/-1.20 and 86.13+/-2.31) with IC50 of 64 and 65 microg/mL, respectively, were observed for compound VII. Molecular docking studies also supported the binding of compound VI and VII with the target enzyme. The para-hydroxyl group of the phenolic moiety is formed hydrogen bonds with the active site water molecule and the side chain carbonyl and hydroxyl residues of enzyme. Conclusion: The isolated compounds inhibited the DPPH and ABTS-free radicals, and AChE and BChE enzymes. It was concluded that these compounds could be used in relieving the oxidative stress and pathological symptoms associated with excessive hydrolysis of acetyl and butyryl choline. The results of the study were supported by docking studies for compounds VI and VII.
ESTHER : Ul Bari_2019_Drug.Des.Devel.Ther_13_3029
PubMedSearch : Ul Bari_2019_Drug.Des.Devel.Ther_13_3029
PubMedID: 31692531