Synthesis and evaluation of the trypanocidal activity of a series of 1,3,4-thiadiazoles derivatives of R-(+)-limonene benzaldehyde-thiosemicarbazones

摘要

In this study, we synthesized a series of 1,3,4-thiadiazole derivatives of R-(+)-limonene benzaldehyde-thiosemicarbazones (2a-k). We also determined the cytotoxicity in LLCMK2 cells and the activity against epimastigote and trypomastigote forms of Trypanosoma cruzi, of these synthetic compounds and also of a series of 1,3,4-thiadiazole without the monoterpene R-(+)-limonene (4a-k). 1,3,4-Thiadiazole compounds showed significant trypanocidal activity and a high selectivity indexes. The vast majority of the monoterpene derivatives, substituted by R-(+)-limonene, presented better anti-T. cruzi activity than the non-substituted compounds. Regarding the cytotoxic profile, the compounds without the monoterpene R-(+)-limonene were, in general, less toxic. The present findings indicate that the 1,3,4-thiadiazoles derivatives of R-limonene have potential trypanocidal activity that justify further studies to better understand the mechanism of action of these substances on T. cruzi.