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

In the presented manuscript, a new series of 2-[4-methoxy-3-(5-substituted phenyl-[1,3,4]oxadiazol-2-ylmethoxy)-phenyl]-benzothiazoles (<b>6a-n</b>) have been synthesized and studied <i>in vivo</i> and <i>in silico</i> for their anticonvulsant potential. Maximum electroshocks (MES) and subcutaneous pentylenetetrazol (scPTZ) models have been used for <i>in vivo</i> anticonvulsant activity. Auto Dock 4.2 software was used for <i>in silico</i> 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. <i>In vivo</i> and <i>In silico</i> studies proved that among all the synthesized compounds, <b>6f, 6h, 6j,</b> and <b>6l</b> were the most potent with no neurotoxicity as compared to conventional drugs (phenytoin and phenobarbital). The <i>in silico</i> 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.