Abstract
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•Compounds 5c, 5g &6c have optimum in-vivo antiepileptic activities without neurotoxicity.•GABA modulatory effects-5c, 5g &6c showed encouraging inhibitory results against GABA AT.•Docking studies-5c binds strongly in a mode similar to standard drug vigabatrin.•Results of in vitro inhibitions are consistent with in vivo seizure protection.•Toxicity studies-no overt toxicity was observed for synthesized compounds.
In the present study, a series of newer benzothiazole derivatives containing thiazolidin-4-one (5a-g) and azetidin-2-one (6a-g), were synthesized by the cyclization of benzothiazolyl arylidene hydrazine carboxamide derivatives with thioglycolic acid and chloroacetyl chloride, respectively. Results of in vivo anticonvulsant screening revealed that compounds having 2,4-dicholoro (5c and 6c) and 4-nitro substituent (5g) at the phenyl ring have promising anticonvulsant activities without any neurotoxicity. Selected compounds were also evaluated for their in vitro GABA AT inhibition. The results indicated that compound 5c (IC50 15.26 μM) exhibited excellent activity as compared to the standard drug vigabatrin (IC50 39.72 μM) suggesting the potential of these benzothiazole analogues as new anticonvulsant agents.