Protease Inhibitors with Antileishmanial Activity

Rosangela      Maria de Araujo Soares; Anna      Lea Silva Barreto; Jose      Alexandre Curvelo; Maristela      Barbosa Portela

Abstract

Proteases make up the largest class of enzymes, with more than 1600 proteases identified from over 1700 organisms. These proteases participate in numerous physiological and pathological processes. In Leishmania, these enzymes play important roles during their life cycle, and in different steps of the microorganism-host interplay. They have become important targets for the rational development of drugs. Proteolytic enzyme activity is closely regulated in many ways, including substrate selectivity, specific cellular location, and it can also be regulated by specific synthetic inhibitors. Protease inhibitor interactions are involved in the regulation of processes such as protein digestion, various physiological and pathological processes and microbial diseases. There are pathological conditions in which uncontrolled proteolytic activity of exogenous proteases derived from infectious agents such as protozoa play a role in the onset and perpetuation of infection, making protease inhibitors potentially applicable as therapeutic agents in the battle against these diseases. Current chemotherapy of leishmaniasis still relies on drugs, which have limited efficiency, toxic side effects and now the emergence of drug resistance. Here in this work some aspects of the relation between antileishmanial and protease inhibitor activities are discussed.

Keywords: Leishmania, protease, inhibitors, leishmaniasis, microorganism-host interplay, Rational development, chemotherapu, drug resistance, proteolytic enyme, synthetic inhibtors