Design, synthesis, biological evaluation and molecular modeling studies of novel eugenol esters as leishmanicidal agents

Abstract

Leishmaniasis is a neglected pathology with a high incidence worldwide, and is a governmental health issue due to the increased morbidity and mortality associated with the disease and a scarce therapeutic arsenal. Cysteine proteases have been investigated as targets for new drugs because they are essential in the infectivity of the parasite during its interaction with the host and in its nutrition. This study aimed to identify compounds with leishmanicidal activity, by synthesis of compounds, in vitro evaluation of their biological activity and using molecular modeling and bioinformatics tools. The study of biological activity demonstrated that one compound showed inhibitory activity against the enzyme rCPB 2.8 at a concentration of 100 μmol L-1. Activation of the enzyme rCPB 2.8 by other 4 compounds was also verified, which may be related to the interaction of these compounds with an allosteric site on the enzyme.