Sintese e avaliação de atividade tripanocida de novos heterociclos da classe dos 1,2,4-OXADIAZÓIS, derivados e análogos da amida natural piperina

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. Using bioisosterism as a strategy for molecular modification, we describe here the design, synthesis and antiparasitic evaluation of class of derivatives of 1,2,4-oxadiazole. The key step of the synthetic strategy used involved the SNAC reaction of the benzamidoxima with acid chlorides followed by cyclization, which allowed the preparation of eight new 1,2,4-oxadiazole The evaluation of the toxic activity of these new derivatives against epimastigote form of T. cruzi confirmed the bioisosteric relationship between the natural amide and the new products prepared, showing the oxadiazole 55 direct derived from piperine, as the most active compound in the series.