Análise de novos compostos orgânicos sintéticos em formas promastigotas de Leishmania (Leishmania) amazonensis: potencial citotóxico e interações in silico

Abstract

Leishmaniasis is a neglected tropical disease caused by protozoa of the genus Leishmania. This disease has two main forms: visceral leishmaniasis and cutaneous leishmaniasis. In Brazil, one of the main species responsible for the latter is Leishmania (L.) amazonensis. Its treatment involves drugs that are highly toxic to the human body, and there are reports of strains resistant to standard treatments, making it necessary to develop new leishmanicidal alternatives. This study aimed to investigate the cytotoxic potential of three synthetic compounds against promastigote forms of L. (L.) amazonensis and in murine macrophages, and to conduct in silico investigations to identify a potential protein target for these compounds. The results showed high cytotoxicity and selectivity of the tested compounds, with compound RMS25 standing out, exhibiting an IC50 of 1.194 μM and a selectivity of 20.335. The application of docking and molecular dynamics techniques to the selected protein, Glycogen Synthase Kinase 3 from L. (L.) amazonensis, indicated favorable results for compound RMS25, such as high complex stability, consistent protein-ligand interactions, and low binding energy, comparable to a reference inhibitor.