Synthesis and biological evaluation of benzothiazole-6-carbohydrazide derivatives as antiparasitic agents

Abstract

A series of N´-substituted-2-(5-nitrofuran or 5-nitrothiophen-2-yl)-3h-benzo[d]thiazole-6-carbohydrazide derivatives were synthesized and investigated for their abilities to inhibit B-hematin formation, hemoglobin proteolysis and for their antimalarial efficacy in rodent Plasmodium berghei. Moreover, we investigated the effect on the viability of Trypanosoma cruzi and Leishmania braziliensis in vitro. We performed a scan to evaluate the cytotoxic effects against two non tumourogenic cell lines. We found that compounds 5a, 6a, and 6g were the most promising as inhibitors of B-hematin formation, especial attention should be paid to 6a which also inhibited hemoglobin proteolysis moderately, decreased parasitaemia and prolonged survivals in infected-mice significantly compared to vehicle controls. Finally, we demonstrated that the compound 7f have a profound effect on the viability of T. cruzi (Tulahuen, CL Brener), shown an IC50 values of 7.7 μm and 0.2 μm respectively, without affecting the viability of the host cells. All compounds showed a marginal activity against L. braziliensis. Thus, compounds 6a and 7f showed anti-parasitic efficacy and good safety index