Ahmad A


Full name : Ahmad Ateeq

First name : Ateeq

Mail : Department of Applied Biochemistry, Walter Read Army Institute of Research

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Country : USA

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References (20)

Title : Computational Approaches to Evaluate the Acetylcholinesterase Binding Interaction with Taxifolin for the Management of Alzheimer's Disease - Ahmad_2024_Molecules_29_
Author(s) : Ahmad V , Alotibi I , Alghamdi AA , Ahmad A , Jamal QMS , Srivastava S
Ref : Molecules , 29 : , 2024
Abstract : Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are enzymes that break down and reduce the level of the neurotransmitter acetylcholine (ACh). This can cause a variety of cognitive and neurological problems, including Alzheimer's disease. Taxifolin is a natural phytochemical generally found in yew tree bark and has significant pharmacological properties, such as being anti-cancer, anti-inflammatory, and antioxidant. The binding affinity and inhibitory potency of taxifolin to these enzymes were evaluated through molecular docking and molecular dynamics simulations followed by the MMPBSA approach, and the results were significant. Taxifolin's affinity for binding to the AChE-taxifolin complex was -8.85 kcal/mol, with an inhibition constant of 326.70 nM. It was observed to interact through hydrogen bonds. In contrast, the BChE-taxifolin complex binding energy was observed to be -7.42 kcal/mol, and it was significantly nearly equal to the standard inhibitor donepezil. The molecular dynamics and simulation signified the observed interactions of taxifolin with the studied enzymes. The MMPBSA total free energy of binding for AChE-taxifolin was -24.34 kcal/mol, while BChE-taxifolin was -16.14 kcal/mol. The present research suggests that taxifolin has a strong ability to bind and inhibit AChE and BChE and could be used to manage neuron-associated problems; however, further research is required to explore taxifolin's neurological therapeutic potential using animal models of Alzheimer's disease.
ESTHER : Ahmad_2024_Molecules_29_
PubMedSearch : Ahmad_2024_Molecules_29_
PubMedID: 38338420

Title : Neuroprotective Efficacy of Europinidin in Streptozotocin-Induced Memory Impairment by Modulation of Oxidative Stress, Inflammatory Mediators, and Cholinesterase Activity in Rats - Ahmad_2023_Oxid.Med.Cell.Longev_2023_5248127
Author(s) : Ahmad A
Ref : Oxid Med Cell Longev , 2023 :5248127 , 2023
Abstract : MATERIALS AND METHODS: Oral acute toxicity studies were performed to evaluate the toxicological effects of europinidin in animals. In this study, four different animal groups (n = 6) were used. Group I was the normal control, group II was the STZ-induced diabetes control, group III was STZ + europinidin-treated (10 mg/kg), and group IV was STZ + europinidin-treated (10 mg/kg). The efficacy of europinidin at a dose of 10 mg/kg and 20 mg/kg was studied with single-dose administration of streptozotocin, which experimentally induced memory impairments in Wistar male rats for 38 days. The mean body weight and blood glucose levels were recorded at the initial and end of the study. The two behavioural paradigms (Y-maze and Morris water maze) were performed to evaluate spatial and working memory in rats. The biochemical parameters such as acetylcholinesterase, choline acetyltransferase, superoxide dismutase, glutathione transferase, malonaldehyde, catalase, and nitric oxide level as hallmarks of oxidative stress were measured. Additionally, the proinflammatory parameters were also determined to evaluate the neuroinflammatory responses associated with streptozotocin such as tumor necrosis factor-alpha (TNF-alpha) interleukin-1beta (IL-1beta), interleukin (IL-6), nuclear factor-kappa B (NF-B), interleukin (IL-10), and nuclear factor-erythroid factor 2-related factor 2 (Nrf2) in the perfused brain. RESULTS: The rats in the europinidin-treated group exhibited a significant restoration of body weight and blood glucose level as compared with the streptozotocin control group. Furthermore, europinidin significantly modulated the spatial and working memory in rats, when assessed through behavioural paradigms. Streptozotocin caused a significant alteration in biochemical, neuronal enzymatic, and neuroinflammatory parameters, which were significantly restored to normal levels by europinidin. CONCLUSION: The present study attributed the neuroprotective efficacy of europinidin in experimental animal models by subsiding the several biomarkers of oxidative stress, neuroinflammation, and neuronal enzymatic activities.
ESTHER : Ahmad_2023_Oxid.Med.Cell.Longev_2023_5248127
PubMedSearch : Ahmad_2023_Oxid.Med.Cell.Longev_2023_5248127
PubMedID: 36760351

Title : Structural features, temperature adaptation and industrial applications of microbial lipases from psychrophilic, mesophilic and thermophilic origins - Rabbani_2023_Int.J.Biol.Macromol_225_822
Author(s) : Rabbani G , Ahmad E , Ahmad A , Khan RH
Ref : Int J Biol Macromol , 225 :822 , 2023
Abstract : Microbial lipases are very prominent biocatalysts because of their ability to catalyze a wide variety of reactions in aqueous and non-aqueous media. Here microbial lipases from different origins (psychrophiles, mesophiles, and thermophiles) have been reviewed. This review emphasizes an update of structural diversity in temperature adaptation and industrial applications, of psychrophilic, mesophilic, and thermophilic lipases. The microbial origins of lipases are logically dynamic, proficient, and also have an extensive range of industrial uses with the manufacturing of altered molecules. It is therefore of interest to understand the molecular mechanisms of adaptation to temperature in occurring lipases. However, lipases from extremophiles (psychrophiles, and thermophiles) are widely used to design biotransformation reactions with higher yields, fewer byproducts, or useful side products and have been predicted to catalyze those reactions also, which otherwise are not possible with the mesophilic lipases. Lipases as a multipurpose biological catalyst have given a favorable vision in meeting the needs of several industries such as biodiesel, foods, and drinks, leather, textile, detergents, pharmaceuticals, and medicals.
ESTHER : Rabbani_2023_Int.J.Biol.Macromol_225_822
PubMedSearch : Rabbani_2023_Int.J.Biol.Macromol_225_822
PubMedID: 36402388

Title : Molecular docking, synthesis and biological evaluation of phenacyl derivatives of 9-aminoacridine as anti-Alzheimer's agent - Munawar_2020_Pak.J.Pharm.Sci_33_659
Author(s) : Munawar R , Mushtaq N , Ahmad A , Saeed SMG , Usmani S , Akhtar S , Saify ZS , Arif M , Akram A
Ref : Pak J Pharm Sci , 33 :659 , 2020
Abstract : Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder mainly characterized by progressive deterioration of memory and impaired cognitive function. The most promising approach for symptomatic relief of AD is to inhibit acetylcholinesterase (AChE). On the basis of this approach in-house library of 9-aminoacridine derivatives were constructed and allowed to docked against human acetylcholinesterase (hAChE) (PDB ID: 4EY7), using MOE 2018.01 and PyRx 0.9.2 (AutoDock Vina). Top ranked and best fitted molecules were synthesized by targeting the 9-amino group of aminoacridine with substituted phenacyl halides. Anti-Alzheimer's potential was checked by in vitro AChE inhibition, antioxidant activity (DPPH scavenging ability) and fibril disaggregation. Subjected ligands suggested as promising multitargeted candidate with pronounced results in term of IC50 values (AChE inhibition 2.400-26.138muM), however, none of them showed potential towards fibril inhibition.
ESTHER : Munawar_2020_Pak.J.Pharm.Sci_33_659
PubMedSearch : Munawar_2020_Pak.J.Pharm.Sci_33_659
PubMedID: 32276912

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 : 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 : Gene structure and comparative study of two different plastic-degrading esterases fromRoseateles depolymeransstrain TB-87 - Ahmad_2019_Polym.Degrad.Stab_164_109
Author(s) : Ahmad A , Tsutsui A , Iijim S , Suzuki T , Shaha AA , Nakajima-kambe T
Ref : Polymer Degradation and Stability , 164 :109 , 2019
Abstract : The structures of two genes fromRoseateles depolymeransstrain TB-87 encoding the esterases Est-H andEst-L, which can degrade aliphatic-aromatic copolyesters, were annotated. Two open reading frames(ORFs) consisting of 1083 bp and 870 bp nucleotides, corresponding toest-Handest-L, encoding enzymesof 290 and 289 amino acids, respectively, were predicted. In addition, another ORF consisting of 735 bpencoding a chaperone-like protein (Est-Ch) of 244 amino acids was identified in the intergenic region ofest-Handest-L. The presence of a promoter region upstream ofest-Hand the absence of a terminatorregion downstream of the ORF and vice versa forest-Ch, suggests thatest-Handest-Chare poly-cistronically expressed. A homology search for Est-H and Est-L revealed homology with plastic degradingenzymes, such as esterases and cutinases, while Est-Ch showed homology with a bacterial lipasechaperone. As consensus lipase sequences (-Gly-His-Ser-Met-Gly-) were observed in these enzymes, Est-H and Est-L were hypothesized to be hydrolases with serine (Ser) in their active center. Three-dimensional structures of Est-H and Est-L without their putative signal sequences were constructedusing Est119 fromThermobifida albastrain AHK119 as the template; the structures and positions of thecatalytic triad (Ser, Asp, His) active centers were similar to those of Est119. A mutant strain in which theannotated esterase-encoding genes were disrupted using a homologous recombination method lost theability to form a clear zone on poly(butylene succinate-co-adipate (PBSA) emulsion-overlaid nutrientagar plates. Characterization of the esterases from strain TB-87 could contribute to the development ofnovel biodegradable plastics with unique properties such as recyclable monomers
ESTHER : Ahmad_2019_Polym.Degrad.Stab_164_109
PubMedSearch : Ahmad_2019_Polym.Degrad.Stab_164_109
Gene_locus related to this paper: 9burk-OWQ89612 , 9acto-d4q9n1 , 9burk-EstL , 9burk-a0a0u3lpw8

Title : Anti-Alzheimer's Studies on beta-Sitosterol Isolated from Polygonum hydropiper L - Ayaz_2017_Front.Pharmacol_8_697
Author(s) : Ayaz M , Junaid M , Ullah F , Subhan F , Sadiq A , Ali G , Ovais M , Shahid M , Ahmad A , Wadood A , El-Shazly M , Ahmad N , Ahmad S
Ref : Front Pharmacol , 8 :697 , 2017
Abstract : The family Polygonaceae is known for its traditional use in the management of various neurological disorders including Alzheimer's disease (AD). In search of new anti-AD drugs, beta-sitosterol isolated from Polygonum hydropiper was subjected to in vitro, in vivo, behavioral and molecular docking studies to confirm its possibility as a potential anti-Alzheimer's agent. The in vitro AChE, BChE inhibitory potentials of beta-sitosterol were investigated following Ellman's assay. The antioxidant activity was tested using DPPH, ABTS and H2O2 assays. Behavioral studies were performed on a sub-strain of transgenic mice using shallow water maze (SWM), Y-maze and balance beam tests. beta-sitosterol was tested for in vivo inhibitory potentials against cholinesterase's and free radicals in the frontal cortex (FC) and hippocampus (HC). The molecular docking study was performed to predict the binding mode of beta-sitosterol in the active sites of AChE and BChE as inhibitor. Considerable in vitro and in vivo cholinesterase inhibitory effects were observed in the beta-sitosterol treated groups. beta-sitosterol exhibited an IC50 value of 55 and 50 mug/ml against AChE and BChE respectively. Whereas, the activity of these enzymes were significantly low in FC and HC homogenates of transgenic animals. Molecular docking studies also support the binding of beta-sitosterol with the target enzyme and further support the in vitro and in vivo results. In the antioxidant assays, the IC50 values were observed as 140, 120, and 280 mug/ml in the DPPH, ABTS and H2O2 assays respectively. The free radicals load in the brain tissues was significantly declined in the beta-sitosterol treated animals as compared to the transgenic-saline treated groups. In the memory assessment and coordination tasks including SWM, Y-maze and balance beam tests, beta-sitosterol treated transgenic animals showed gradual improvement in working memory, spontaneous alternation behavior and motor coordination. These results conclude that beta-sitosterol is a potential compound for the management of memory deficit disorders like AD.
ESTHER : Ayaz_2017_Front.Pharmacol_8_697
PubMedSearch : Ayaz_2017_Front.Pharmacol_8_697
PubMedID: 29056913

Title : Antioxidant, Acetylcholinesterase, Butyrylcholinesterase, and alpha-glucosidase Inhibitory Activities of Corchorus depressus - Afzal_2017_Pharmacogn.Mag_13_647
Author(s) : Afzal S , Chaudhry BA , Ahmad A , Uzair M , Afzal K
Ref : Pharmacogn Mag , 13 :647 , 2017
Abstract : Background: Corchorus depressus (Cd) commonly known as Boa-phalee belonging to the family Tiliaceae having 50 genera and 450 species. Cd is not among the studied medicinal agent despite its potential in ethnopharmacology. Objectives: The present study investigated antioxidant, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha-glucosidase inhibitory activities of Cd. The dichloromethane and methanolic extracts of the Cd were evaluated for biological activities such as antioxidant and enzyme inhibitory activities of AChE, BChE, and alpha-glucosidase. Materials and Methods: Antioxidant activity was evaluated by measuring free radical scavenging potential of Cd using 1,1-diphenyl-2-picrylhydrazyl. Enzyme inhibition activities were done by measuring optical density. Results: The methanol extract of roots of Cd showed potential free radical scavenging activity 99% at concentration 16.1 mug/ml. AChE was inhibited by aerial part of dichloromethane fraction by 46.07% +/- 0.45% while dichloromethane extracts of roots of Cd possessed significant activity against BChE with 86% inhibition compared with standard drug Eserine at concentration 0.5 mg/ml. The dichloromethane extract of roots of Cd showed 79% inhibition against alpha-glucosidase enzyme activity with IC50 62.8 +/- 1.5 mug/ml. Conclusion: These findings suggest Cd as useful therapeutic option as antioxidant and inhibition of AChE, BChE, and alpha-glucosidase activities. SUMMARY: The aerial parts and roots of Corchorus depressus (Cd) were extracted in dichloromethane and methanolThe extract of roots of Cd showed free radical scavenging activity 99% at concentration 16.1 mg/ml, Ach inhibition by aerial parts of dichloromethane fraction by 46.07%, and 79% inhibition against a-glucosidase enzyme activity with IC50 62.8 +/- 1.5 mg/mlThe dichloromethane and methanolic extracts of Cd exhibited antioxidant inhibition of acetyl cholinesterase, butyrylcholinesterase, and a-glucosidase activities. Abbreviations used: DPPH: 1,1-diphenyl-2-picrylhydrazyl, Cd: Corchorus depressus, AChE: Acetylcholinesterase, BChE: Butyrylcholinesterase, AD: Alzheimer's disease.
ESTHER : Afzal_2017_Pharmacogn.Mag_13_647
PubMedSearch : Afzal_2017_Pharmacogn.Mag_13_647
PubMedID: 29200727

Title : Prediction of Anti-Diabetic Drugs as Dual Inhibitors Against Acetylcholinesterase and Beta-Secretase: A Neuroinformatics Study - Shaikh_2016_CNS.Neurol.Disord.Drug.Targets_15_1216
Author(s) : Shaikh S , Rizvi SM , Suhail T , Shakil S , Abuzenadah AM , Anis R , Naaz D , Dallol A , Haneef M , Ahmad A , Choudhary L
Ref : CNS Neurol Disord Drug Targets , 15 :1216 , 2016
Abstract : An increasing number of research evidences indicate linkage between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD); the two most common diseases of aging. In addition, T2DM and AD also share some common pathophysiological features. Therefore, dual therapy that targets both the diseases can be regarded as a beneficial approach. Acetylcholinesterase (AChE) and beta-secretase (BACE) have been considered as potential therapeutic targets for AD. Accordingly, the piece of work presented here describes the binding of anti-diabetic drugs (Jardiance, Suiny and Nesina) with AChE and BACE so as to further investigate connecting bridges concerning the treatment of these two diseases. We have used "Autodock 4.2" for docking experiments. Both, hydrogen bond and hydrophobic interactions were found to be involved in the proper positioning of these diabetic drugs within the catalytic site (CAS) of AChE and BACE enzymes to permit docking. Free energy of binding (DeltaG) for 'Jardiance-AChE', 'uiny-AChE' and 'Nesina-AChE' CAS interactions were found to be -9.21, -7.32 and -10.66 kcal/mol, respectively; while for 'Jardiance-BACE', 'Suiny -BACE' and 'Nesina-BACE' CAS interactions the same were determined to be -8.91, -8.58 and -10.40 kcal/mol, respectively. Hence, these diabetic drugs might act as potent dual inhibitors for the treatment of diabetes-associated neurological disorders. Consequently, the results described herein may form the basis of future dual therapy against the same.
ESTHER : Shaikh_2016_CNS.Neurol.Disord.Drug.Targets_15_1216
PubMedSearch : Shaikh_2016_CNS.Neurol.Disord.Drug.Targets_15_1216
PubMedID: 27697060

Title : Kinetics and Molecular Docking Study of an Anti-diabetic Drug Glimepiride as Acetylcholinesterase Inhibitor: Implication for Alzheimer's Disease-Diabetes Dual Therapy - Rizvi_2016_Neurochem.Res_41_1475
Author(s) : Rizvi SM , Shaikh S , Naaz D , Shakil S , Ahmad A , Haneef M , Abuzenadah AM
Ref : Neurochem Res , 41 :1475 , 2016
Abstract : At the present time, treatment of two most common degenerative disorders of elderly population i.e., Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD) is a major concern worldwide. As there are several evidences that proved strong linkages between these two disorders, the idea of using dual therapeutic agent for both the diseases might be considered as a good initiative. Earlier reports have revealed that oral anti-diabetic drugs such as peroxisome proliferator activated receptor gamma (PPARgamma) agonists (thiazolidinediones) when used in T2DM patients suffering from AD showed improved memory and cognition. However, the underlying mechanism still needs to be deciphered. Therefore, the present study was carried out to find whether glimepiride, an oral antidiabetic drug which is a PPARgamma agonist could inhibit the activity of acetylcholine esterase (AChE) enzyme. Actually, AChE inhibitors seize the breakdown of acetylcholine which forms the main therapeutic strategy for AD. Here, glimepiride showed dose dependent inhibitory activity against AChE enzyme with IC50 value of 235 muM. Kinetic analysis showed competitive inhibition, which was verified by in silico docking studies. Glimepiride was found to interact with AChE enzyme at the same locus as that of substrate acetylcholine iodide (AChI). Interestingly, amino acid residues, Q71, Y72, V73, D74, W86, N87, Y124, S125, W286, F295, F297, Y337, F338 and Y341 of AChE were found to be common for 'glimepiride-AChE interaction' as well as 'AChI-AChE interaction'. Thus the present computational and kinetics study concludes that glimepiride and other thiazolidinediones derivatives could form the basis of future dual therapy against diabetes associated neurological disorders.
ESTHER : Rizvi_2016_Neurochem.Res_41_1475
PubMedSearch : Rizvi_2016_Neurochem.Res_41_1475
PubMedID: 26886763

Title : Novel structural hybrids of pyrazolobenzothiazines with benzimidazoles as cholinesterase inhibitors - Aslam_2014_Eur.J.Med.Chem_78C_106
Author(s) : Aslam S , Zaib S , Ahmad M , Gardiner JM , Ahmad A , Hameed A , Furtmann N , Gutschow M , Bajorath J , Iqbal J
Ref : Eur Journal of Medicinal Chemistry , 78C :106 , 2014
Abstract : Two series of novel pyrazolobenzothiazine-based hybrid compounds were efficiently synthesized starting from saccharin sodium salt. Pyrazolo[4,3-c][1,2]benzothiazine scaffolds were N-arylated by using p-fluorobenzaldehyde, followed by the incorporation of a benzimidazole or similar ring systems by treatment with arylenediamines. These phenylene-connected hybrid compounds were investigated as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BCHE). Compounds 12d and 12k were the most potent AChE inhibitors with IC50 values of 11 and 13 nM, respectively, while 6j (IC50 = 17 nM) proved to be the most active inhibitor against BCHE with remarkable selectivity for BCHE over AChE. Molecular docking studies were also performed on human AChE and BCHE to suggest possible binding modes in which the inhibitor's extended structure is accommodated along the active site gorge of both enzymes.
ESTHER : Aslam_2014_Eur.J.Med.Chem_78C_106
PubMedSearch : Aslam_2014_Eur.J.Med.Chem_78C_106
PubMedID: 24681070

Title : Effects of the Total Alkaloidal Extract of Murraya koenigii Leaf on Oxidative Stress and Cholinergic Transmission in Aged Mice - Mani_2013_Phytother.Res_27_46
Author(s) : Mani V , Ramasamy K , Ahmad A , Wahab SN , Jaafar SM , Kek TL , Salleh MZ , Majeed AB
Ref : Phytother Res , 27 :46 , 2013
Abstract : Alzheimer's disease (AD) is characterized by signs of major oxidative stress and the loss of cholinergic cells. The present study was designed to investigate the role of the total alkaloidal extract from Murraya koenigii (MKA) leaves on age related oxidative stress and the cholinergic pathway in aged mice. Ascorbic acid (100 mg/kg, p.o.) was used as a standard drug. The MKA improved the level of protective antioxidants such as glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase (GRD), superoxide dismutase (SOD) and catalase (CAT) in brain homogenate at higher doses (20 and 40 mg/kg, p.o.). Moreover, a dose dependent decline was noted in lipid peroxidation (LPO) and the nitric oxide assay (NO) at all doses of MKA (10, 20 and 40 mg/kg, p.o.). Interestingly, significant progress was noted with the supplementation of MKA by an improvement of the acetylcholine (ACh) levels and a reduction in the acetylcholinesterase (AChE) activity in aged mouse brain. In addition, a significant elevation of serum albumin (ALBU), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST) and total protein as well as a decline in creatinine, total cholesterol, urea nitrogen and glucose levels with MKA also ameliorated the hepatic and renal functions in normal ageing process. The results showed the possible utility of Murraya koenigii leaves in neuroprotection against neurodegenerative disorders such as Alzheimer's disease. Copyright (c) 2012 John Wiley & Sons, Ltd.
ESTHER : Mani_2013_Phytother.Res_27_46
PubMedSearch : Mani_2013_Phytother.Res_27_46
PubMedID: 22447662

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 : Total isoflavones from soybean and tempeh reversed scopolamine-induced amnesia, improved cholinergic activities and reduced neuroinflammation in brain - Ahmad_2013_Food.Chem.Toxicol_65C_120
Author(s) : Ahmad A , Ramasamy K , Jaafar SM , Majeed AB , Mani V
Ref : Food & Chemical Toxicology , 65C :120 , 2013
Abstract : The present study was undertaken to compare the neuroprotective effects between total isoflavones from soybean and tempeh against scopolamine-induced cognitive dysfunction. Total isoflavones (10, 20 and 40mg/kg) from soybean (SI) and tempeh (TI) were administered orally to different groups of rats (n=6) for 15days. Piracetam (400mg/kg, p.o.) was used as a standard drug while scopolamine (1mg/kg, i.p.) was used to induce amnesia in the animals. Radial arm and elevated plus mazes served as exteroceptive behavioural models to measure memory. Brain cholinergic activities (acetylcholine and acetylcholinesterase) and neuroinflammatory activities (COX-1, COX-2, IL-1beta and IL10) were also assessed. Treatment with SI and TI significantly reversed the scopolamine effect and improved memory with TI group at 40mg/kg, p.o. exhibiting the best improvement (p<0.001) in rats. The TI (10, 20 and 40mg/kg, p.o.) significantly increased (p<0.001) acetylcholine and reduced acetylcholinesterase levels. Meanwhile, only a high dose (40mg/kg, p.o.) of SI showed significant improvement (p<0.05) in the cholinergic activities. Neuroinflammation study also showed that TI (40mg/kg, p.o.) was able to reduce inflammation better than SI. The TI ameliorates scopolamine-induced memory in rats through the cholinergic neuronal pathway and by prevention of neuroinflammation.
ESTHER : Ahmad_2013_Food.Chem.Toxicol_65C_120
PubMedSearch : Ahmad_2013_Food.Chem.Toxicol_65C_120
PubMedID: 24373829

Title : Toxicological effect of herbicides (diuron and bentazon) on snake venom and electric eel acetylcholinesterase - Ahmed_2012_Bull.Environ.Contam.Toxicol_89_229
Author(s) : Ahmed M , Latif N , Khan RA , Ahmad A
Ref : Bulletin of Environmental Contamination & Toxicology , 89 :229 , 2012
Abstract : The toxicological effects of the active ingredients of the herbicides diuron and bentazon on the activity of acetylcholinesterase (AChE) of krait (Bungarus sindanus) venom and electric eel (Electrophorus electricus) were studied. The diuron and entazon caused non-competitive inhibition of AChE from both species. For the venom AChE, the calculated IC50 for diuron and bentazon were found to be 3.25 and 0.14 muM, while for eel AChE, the respective IC50 values were 3.6 and 0.135 muM. In comparison, bentazon was a more potent inhibitor than diuron of AChE from both species. The insecticide lindane did not have any inhibitory effect on AChE activity in either species, even when tested at high concentrations (200-800 muM).
ESTHER : Ahmed_2012_Bull.Environ.Contam.Toxicol_89_229
PubMedSearch : Ahmed_2012_Bull.Environ.Contam.Toxicol_89_229
PubMedID: 22653306

Title : Toxicological effect of N, N, N', N'-tetramethylethylene on rat brain acetylcholinesterase - Ahmed_2012_Toxicol.Ind.Health_30_415
Author(s) : Ahmed M , Latif N , Khan RA , Ahmad A , Schetinger MR , Rocha JB
Ref : Toxicol Ind Health , 30 :415 , 2012
Abstract : N, N, N', N'-tetramethylethylenediamine (TEMED) is extensively used for initiating polymerization of acrylamide and bisacrylamide gel for electrophoresis and for inorganic complex structure formation. The present study evaluates the toxicological effect of TEMED on structures of rat brain acetylcholinesterase (AChE) activity. In vitro study showed that the Ki values for striatum, cortex, cerebellum and hypothalamus were found to be 1.24, 1.4, 1.45 and 1.47 mM. Kinetics studies indicated that TEMED caused mixed type of inhibition that is a combination of competitive and noncompetitive inhibition in striatum, cortex, hypothalamus and cerebellum. The result showed that km increased and V max decreased with increase in TEMED concentration. The IC50 values calculated for striatum, cortex, cerebellum and hypothalamus were found to be as 0.92, 0.92, 1.44 and 1.42 mM. The present study indicates that TEMED is a toxicant for brain via inhibition of AChE. Therefore, proper precaution should be made during its handling.
ESTHER : Ahmed_2012_Toxicol.Ind.Health_30_415
PubMedSearch : Ahmed_2012_Toxicol.Ind.Health_30_415
PubMedID: 22914266

Title : Protective effects of total alkaloidal extract from Murraya koenigii leaves on experimentally induced dementia - Mani_2012_Food.Chem.Toxicol_50_1036
Author(s) : Mani V , Ramasamy K , Ahmad A , Parle M , Shah SA , Majeed AB
Ref : Food & Chemical Toxicology , 50 :1036 , 2012
Abstract : Dementia is a syndrome of gradual onset and continuous decline of higher cognitive functioning. It is a common disorder in older persons and has become more prevalent today. The fresh leaves of Murraya koenigii are often added to various dishes in Asian countries due to the delicious taste and flavor that they impart. These leaves have also been proven to have health benefits. In the present study, the effect of total alkaloidal extract from M. koenigii leaves (MKA) on cognitive functions and brain cholinesterase activity in mice were determined. In vitro beta-secretase 1 (BACE1) inhibitory activity was also evaluated. The total alkaloidal extract was administered orally in three doses (10, 20 and 30 mg/kg) for 15 days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine-, and ageing-induced amnesia served as the interoceptive behavioral models. MKA (20 and 30 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. Furthermore, the same doses of MKA reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Interestingly, the brain cholinesterase activity was also reduced significantly by total alkaloidal extract of M. koenigii leaves. The IC50 value of MKA against BACE1 was 1.7 mug/mL. In conclusion, this study indicates MKA to be a useful remedy in the management of Alzheimer's disease and dementia.
ESTHER : Mani_2012_Food.Chem.Toxicol_50_1036
PubMedSearch : Mani_2012_Food.Chem.Toxicol_50_1036
PubMedID: 22142688

Title : Isolation of four new pterocarpans from Zygophyllum eurypterum (Syn. Z. atriplicoides) with enzyme-inhibition properties - Ahmad_2006_Chem.Biodivers_3_996
Author(s) : Ahmad VU , Iqbal S , Nawaz SA , Choudhary MI , Farooq U , Ali ST , Ahmad A , Bader S , Kousar F , Arshad S , Tareen RB
Ref : Chem Biodivers , 3 :996 , 2006
Abstract : Four new pterocarpans, atricarpan A (=(-)-1,2-dihydroxy-4-(hydroxymethyl)-3,9-dimethoxypterocarpan; 1), atricarpan B (=(-)-2,3-ethylenedioxy)-1,4-dihydroxy-9-methoxypterocarpan; 2), atricarpan C (=(-)-1,9-dimethoxypterocarpan-3-carboxylic acid; 3), and atricarpan D (=(-)-2,9-dimethoxy-4-(5-oxohexyl)pterocarpan; 4) were isolated from the BuOH extract of the whole plant of Zygophyllum eurypterum. The structure elucidations of those compounds were based primarily on 1D- and 2D-NMR analysis, including COSY, HMBC, and HMQC correlations. Compounds 1-4 also inhibited butyrylcholinesterase (BChE; EC enzyme in a concentration-dependent manner with IC(50) values between 12.5-65.0 microM. Similarly, compounds 1 and 4 inhibited lipoxygenase (LOX; EC and acetylcholinesterase (AChE; EC enzymes with IC50 values of 13.5 and 20.5 muM, respectively.
ESTHER : Ahmad_2006_Chem.Biodivers_3_996
PubMedSearch : Ahmad_2006_Chem.Biodivers_3_996
PubMedID: 17193332

Title : 6-Methyl-6-azabicyclo[3.2.1]octan-3 alpha-ol 2,2-diphenylpropionate (azaprophen), a highly potent antimuscarinic agent - Carroll_1987_J.Med.Chem_30_805
Author(s) : Carroll FI , Abraham P , Parham K , Griffith RC , Ahmad A , Richard MM , Padilla FN , Witkin JM , Chiang PK
Ref : Journal of Medicinal Chemistry , 30 :805 , 1987
Abstract : The synthesis and antimuscarinic properties of 6-methyl-6-azabicyclo[3.2.1]octan-3 alpha-ol 2,2-diphenylpropionate (1, azaprophen) are described. Azaprophen is 50 times more potent than atropine as an antimuscarinic agent as measured by the inhibition of acetylcholine-induced contraction of guinea pig ileum and is more than 1000 times better than atropine in its ability to block alpha-amylase release from pancreatic acini cells induced by carbachol. In addition, azaprophen is 27 times more potent than atropine as an inhibitor of binding of [N-methyl-3H]scopolamine to muscarinic receptors, with human IMR-30 neuroblastoma cells. The potencies of azaprophen and atropine in altering operant behavior were similar. The structural features of 1 are compared to the standard anticholinergic drugs atropine and quinuclidinyl benzilate by using energy calculations and molecular modelling studies. A modification of the pharmacophore model hypothesis for cholinergic agents is suggested.
ESTHER : Carroll_1987_J.Med.Chem_30_805
PubMedSearch : Carroll_1987_J.Med.Chem_30_805
PubMedID: 3494849