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Study of anthranil hydrazides as potential growth inhibitory activity of Leishmania amazonensis

Grant number: 19/20686-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2019
Effective date (End): November 30, 2020
Field of knowledge:Biological Sciences - Biochemistry - Biochemistry of Microorganisms
Principal researcher:Edson Roberto da Silva
Grantee:Barbara Hild de Jesus
Home Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil

Abstract

Caused by protozoans of the Leishmania genus, leishmaniasis is a group of neglected diseases that afflicts thousands of people worldwide, where its most severe form, visceral leishmaniasis if left untreated, has a high mortality rate. They have as a vector the sand flies, which inoculate the promastigote form of the parasite in the host and, within macrophages, assume the amastigote form, initiating their reproduction, cell disruption and continuity of the parasite cycle. Although there are some chemotherapeutic agents against this disease, they do not have expected efficacy in the treatment, as they cause significant side effects due to their cytotoxicity, low response to co-infections, variation in sensitivity between species and several other unwanted results, which contribute to the resistance of these parasites. Thus, there is a need for new research for the production of new drugs. Leishmania arginase has been studied as a target for the development of new treatments, as it is a precursor of polyamine production, responsible for the elimination of reactive oxygen species and nitrogen free radicals produced by macrophages to eliminate the parasite. An enzyme of this polyamine pathway is targeted by the drug eflornithine, used to combat the "sleeping sickness" parasite, and from it, a prototype containing the pharmacophoric group phenylhydrazides, which have the potential to inhibit Leishmania arginase, was developed. The anthranylhydrazides, derived from phenylhydrazides, presented in screening at 10 ¼M a good inhibition of parasite growth. Thus this project aims to characterize the action of these new compounds in a model of experimental murine macrophage infection.

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