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Computational and Pharmacological Investigation of (E)-2-(4-Methoxybenzylidene)Cyclopentanone for Therapeutic Potential in Neurological Disorders.

ABSTRACT: Purpose:This study involved the computational and pharmacological evaluation of (E)-2-(4-methoxybenzylidene)cyclopentan-1-one (A2K10). Methods:In silico studies were conducted through virtual screening. Morris water and Y-maze tests were conducted to evaluate Alzheimer's disease. Acute epilepsy haloperidol,and hyperalgesia were used to calculate the epilepsy model, with Parkinson's disease and mechanical allodynia at a dose of 1-10 mg/kg in the mouse model. Results:A2K10 exhibited the highest binding affinity against ?7 nicotinic acetylcholine receptors (-256.02 kcal/mol). A2K10 decreased escape latency in the Morris water test during different trials. In the Y-maze test, A2K10 dose-dependently increased spontaneous alteration behavior, with maximum effect of 75.5%±0.86%. Furthermore, A2K10 delayed onset of pentylenetetrazole-induced myoclonic jerks and tonic-clonic seizures and decreased duration of tonic-clonic convulsions in mice, with maximum effect of 93.8±5.30, 77.8±2.91, and 12.9±1.99 seconds, respectively. In the haloperidol-induced Parkinson's disease model, A2K10 significantly prolonged hanging time and reduced tardive dyskinesia. Moreover, A2K10 extended latency in hot-plate hyperalgesia and increased the paw-withdrawal threshold in mechanical allodynia. In toxicity studies, no mortality was observed. Conclusion:Overall, the results indicated that A2K10 has potential as an anti-Alzheimer's, antiepileptic, antiparkinsonian, and analgesic therapeutic compound.

SUBMITTER: Farooq S

PROVIDER: S-EPMC7490097 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Computational and Pharmacological Investigation of (E)-2-(4-Methoxybenzylidene)Cyclopentanone for Therapeutic Potential in Neurological Disorders.

Farooq Sabah S Khan Arif-Ullah AU Iqbal Muhammad Shahid MS

Drug design, development and therapy 20200907

<h4>Purpose</h4>This study involved the computational and pharmacological evaluation of (E)-2-(4-methoxybenzylidene)cyclopentan-1-one (A2K10).<h4>Methods</h4>In silico studies were conducted through virtual screening. Morris water and Y-maze tests were conducted to evaluate Alzheimer's disease. Acute epilepsy haloperidol,and hyperalgesia were used to calculate the epilepsy model, with Parkinson's disease and mechanical allodynia at a dose of 1-10 mg/kg in the mouse model.<h4>Results</h4>A2K10 ex ...[more]

PMID: 32982169

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Dataset Information

Computational and Pharmacological Investigation of (E)-2-(4-Methoxybenzylidene)Cyclopentanone for Therapeutic Potential in Neurological Disorders.

Publications

Computational and Pharmacological Investigation of (E)-2-(4-Methoxybenzylidene)Cyclopentanone for Therapeutic Potential in Neurological Disorders.

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