Design, synthesis and evaluation of N-(substituted benzothiazol-2-yl)amides as anticonvulsant and neuroprotective

A series of N-(substituted benzothiazol-2-yl)amide derivatives 2a–h and 4a–h were synthesized by the EDC coupling reactions of substituted-benzothiazol-2-amine with 4-oxo-4-phenylbutanoic acid/2-benzoyl benzoic acid and evaluated for their anticonvulsant and neuroprotective effect. N-(6-methoxybenzothiazol-2-yl)-4-oxo-4-phenylbutanamide (2f) emerged as the most effective anticonvulsant with median doses of 40.96 mg/kg (MES ED50), 85.16 mg/kg (scPTZ ED50) and 347.6 mg/kg (TD50). Furthermore, compound 2f displayed promising neuroprotective effect by lowering the levels of MDA and LDH; therefore, it represents a potential lead in search for safer and effective anticonvulsants having neuroprotective effects.

Graphical abstractSome amide derivatives of benzothiazole were prepared and evaluated for their anticonvulsant activity. Compound 2f exhibited promising anticonvulsant activity with neuroprotective effect.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of benzothiazol-2-ylamides 2a–h and 4a–h were synthesized. ► Anticonvulsant activity, neurotoxicity and CNS depressant studies were performed. ► The most active compound 2f showed 40.96 mg/kg ED50 and 8.4 PI in the MES test. ► Compound 2f displayed promising neuroprotective effect by lowering the MDA and LDH levels.