Planejamento, síntese e avaliação da atividade de novos 1,2,4-triazóis, derivados da amida natural piperina, contra formas proliferativas do Trypanosoma cruzi.

Abstract

The work reported herein describes the design, synthesis and the assessment of the trypanocidal activity of thirteen new 1,2,4-triazole-3-thiones obtained from natural piperine, the main constituent of the dry fruits of Piper nigrum (black pepper). It is part of a research program aiming to use abundant and easily available natural products as starting materials for the design and synthesis of new molecules potentially useful as antiparasitic drugs. The design of the variously substituted triazole derivatives was based on the strategies of bioisosterism and molecular hybridization. The thirteen new 1,2,4-triazole were synthesized from the natural amide in four steps with the use of microwave irradiation on overall yields ranging from 32% to 51%. The cyclohexyl substituted derivative showed the best trypanocidal profile on proliferative forms of Trypanosoma cruzi (Y strain), with IC50 values of 18.3 and 8.87 mM against epimastigotes and amastigotes, respectively.