Utilização da piperina como protótipo na síntese de novos anti-chagásicos da classe das 1,3,4-tiadiazólico-2-fenilaminas

Abstract

This work is part of a research project which investigates the utilization of abundant and accessible natural products in the synthesis of new molecules with potential activity against Chagas´ disease. Recent studies carried out in our laboratory showed activity against Trypanosoma cruzi for piperine, a major component of Piper nigrum and for a series of its derivatives and analogues. We herein describe the synthesis and characterization of nine new 1,3,4,-tiadiazolium-2- phenilaminides derived from piperine. We also evaluated their toxic effects against the various evolutive forms of T. cruzi, and also against the host cell (murine macrophages). These results obtained show that the mesoionic hydrochloride MI possesses the best activity profile. Furthermore, MI showed in vivo activity comparable to benzonidazole. The results suggest MI may be a new prototype for use in the development of a new chemotherapeutic agent with high efficiency, which may be employed in the treatment of Chagas´s disease.