Design, Synthesis, In Vivo, and In Silico Evaluation of Benzothiazoles Bearing a 1,3,4-Oxadiazole Moiety as New Antiepileptic Agents

含有 1,3,4-恶二唑部分的苯并噻唑作为新型抗癫痫药物的设计、合成、体内和计算机模拟评估

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作者:Bharti Chauhan, Rajnish Kumar, Salahuddin, Himanshu Singh, Obaid Afzal, Abdulmalik Saleh Alfawaz Altamimi, Mohd Mustaqeem Abdullah, Mohammad Shahar Yar, Mohamed Jawed Ahsan, Neeraj Kumar, Sanjay Kumar Yadav

Abstract

In the presented manuscript, a new series of 2-[4-methoxy-3-(5-substituted phenyl-[1,3,4]oxadiazol-2-ylmethoxy)-phenyl]-benzothiazoles (6a-n) have been synthesized and studied in vivo and in silico for their anticonvulsant potential. Maximum electroshocks (MES) and subcutaneous pentylenetetrazol (scPTZ) models have been used for in vivo anticonvulsant activity. Auto Dock 4.2 software was used for in silico studies, and the targeted protein was 5IOV.sThe antidepressant activity of selected compounds (most active) was determined as a reduction in locomotor activity through an actophotometer. In vivo and In silico studies proved that among all the synthesized compounds, 6f, 6h, 6j, and 6l were the most potent with no neurotoxicity as compared to conventional drugs (phenytoin and phenobarbital). The in silico studies also indicated about different binding interactions of synthetic compounds to localize the binding receptors. The most likely mode of action for these drugs, according to the docking analysis of active compounds with various targets, is their binding to the VGCC and NMDA receptors.

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