Synthesis, Anticonvulsant Activity and Cytotoxicity of Novel Valproic Acid Derivatives

Abstract

Objective: The aim of this work was to construct novel hydrazones and thiosemsicarbazide derivatives of valproic acid. The new targets will be evaluated for their anticonvulsant activity and cytotoxicity effects. Methods: Targets 7a-k, 10. 11 were synthesized starting from valproic acid using benzotriazole activation and hydrazide and thiosemicarbazide chemistry. The anticonvulsant activity was evaluated by pentylenetetrazoleinduced seizures modes using sodium valproate as a standard for comparison of the activity. The compounds with high anticonvulsant activity were subsequently examined for cytotoxicity against HepG2 by MTT assay. Results: The new targets were characterized using 1 HNMR and 13 CNMR and their purity were authenticated by elemental analysis. Four compounds 7e, 7j, 10 and 11 exhibited the most potent anticonvulsant activity associated with low cytotixicity. Conclusion: Compounds 11 exhibited a moderate anticonvulsant activity and a significantly lower cytotoxicity than valproic acid and 5-fluorouracile suggesting that it could be used as a lead for the development of better anticonvulsant drug candidates.