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 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

Acknowledgments

We are grateful to Dr Zia Ud Din for the gift of A2K10. We are thankful to Dr Muzaffar Abbas for his valuable guidance and Komal Naeem for her editorial cooperation.

Disclosure

The authors report no conflicts of interest for this work.