Novel benzothiazole hydrazine carboxamide hybrid scaffolds as potential in vitro GABA AT enzyme inhibitors: Synthesis, molecular docking and antiepileptic evaluation

Bioorganic & Medicinal Chemistry Letters
2019.0

Abstract

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 (IC<sub>50</sub> 15.26 μM) exhibited excellent activity as compared to the standard drug vigabatrin (IC<sub>50</sub> 39.72 μM) suggesting the potential of these benzothiazole analogues as new anticonvulsant agents.

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