Leishmanicidal therapy targeted to parasite proteases

Leishmaniasis is considered a serious public health problem and the current available therapy has several disadvantages, which makes the search for new therapeutic targets and alternative treatments extremely necessary. In this context, this review focuses on the importance of parasite proteases as target drugs against Leishmania parasites, as a chemotherapy approach. Initially, we discuss about the current scenario for the treatment of leishmaniasis, highlighting the main drugs used and the problems related to their use. Subsequently, we describe the inhibitors of major proteases of Leishmania already discovered, such as Compound s9 (aziridine-2,3-dicarboxylate), Compound 1c (benzophenone derivative), Au2Phen (gold complex), AubipyC (gold complex), MDL 28170 (dipeptidyl aldehyde), K11777, Hirudin, diazo-acetyl norleucine methyl ester, Nelfinavir, Saquinavir, Nelfinavir, Saquinavir, Indinavir, Saquinavir, GNF5343 (azabenzoxazole), GNF6702 (azabenzoxazole), Benzamidine and TPCK. Next, we discuss the importance of the protease gene to parasite survival and the aspects of the validation of proteases as target drugs, with emphasis on gene disruption. Then, we describe novel important strategies that can be used to support the research of new antiparasitic drugs, such as molecular modeling and nanotechnology, whose main targets are parasitic proteases. And finally, we discuss possible perspectives to improve drug development. Based on all findings, proteases could be considered potential targets against leishmaniasis. [Display omitted]