Prospecção in vitro de Peptídeos Sintéticos Ricos em Triptofano com Potencial Atividade anti-Leishmania sp.

Abstract

Leishmaniases are a group of diseases caused by protozoa of the genus Leishmania. Because they primarily affect people in developing countries, leishmaniases are considered neglected diseases. In 2020, 70% of reported leishmaniasis cases in the Americas occurred in Brazil, making it one of the endemic diseases with the fastest-growing rates in the country. Therapeutic options for leishmaniases involve the administration of drugs that have various side effects, justifying the need for the development of new medications. Studies involving natural antimicrobial peptides have advanced in silico prediction techniques, generating potential drugs with high selectivity. By rationally designing peptides, in vitro studies can be conducted, reducing the time required for the development of new medications. The aim of this study was to evaluate the in vitro screening of synthetic peptides rich in arginine and tryptophan with potential anti-Leishmania sp. activity. Two peptides rich in arginine and tryptophan, RK8 and RK8-II, were designed, synthesized, and their anti-Leishmania potential was assessed in vitro against promastigote and intracellular amastigote forms of Leishmania amazonensis and promastigotes of Leishmania infantum. RK8-II, with an IC50 of 9.2 µM at 48h, was more active than RK8, with an IC50 of 54.5 μM at 48h. The peptide RK8II also showed low cytotoxicity in red blood cells (CC50 obtained was 22.73 μM), NIH/3T3 cells, and RAW 264.7 cells, indicating that these structures exhibit selective anti-Leishmania activity. Further studies may evaluate the possible targets of these peptides and their feasibility for pre-clinical and clinical applications.