Drug Design, Development and Therapy (Sep 2020)
Computational and Pharmacological Investigation of (E)-2-(4-Methoxybenzylidene)Cyclopentanone for Therapeutic Potential in Neurological Disorders
Abstract
Sabah Farooq,1 Arif-ullah Khan,1 Muhammad Shahid Iqbal2 1Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; 2Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi ArabiaCorrespondence: Arif-ullah KhanRiphah Institute of Pharmaceutical Sciences, Riphah International University, 7th Avenue, Sector G-7/4, Islamabad, PakistanTel +92-51-289-1835-38Fax +92-51-2891471, 2890690Email [email protected]: 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 α7 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.Keywords: computational pharmacology, anti-Alzheimer, antiepileptic, antiparkinsonism , analgesic
