Add time:08/18/2019         Source:sciencedirect.com

Different compounds have been investigated as potent drugs for trypanosomiasis treatment, but no new drug has been marketed in the past 3 decades. 4-Thiazolidinone/thiazole as privileged structures and thiosemicarbazides cyclic analogs are well known scaffolds in novel antitrypanosomal agent design. We present here the design and synthesis of new hybrid molecules bearing thiazolidinone/thiazole cores linked by the hydrazone group with various molecular fragments. Structure optimization led to compounds with phenyl-indole or phenyl-imidazo[2,1-b][1,3,4]thiadiazole moieties showing excellent antitrypanosomal activity towards Trypanosoma brucei brucei and Trypanosoma brucei gambiense. Biological study allowed identifying compounds with the submicromolar levels of IC50, good selectivity indexes and relatively low cytotoxicity upon human primary fibroblasts as well as low acute toxicity.

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