Galato De Octila: Avaliação Da Atividade Antileishmania, Perfil Citotóxico E Análise Da Integridade De Membrana

Abstract

Leishmaniasis is a group of neglected tropical diseases with wide global distribution and high public health impact. Visceral leishmaniasis (VL) stands out for its high lethality when left untreated and is mainly caused by Leishmania donovani and Leishmania infantum. Current treatments are limited by toxicity, high cost, and parasite resistance, highlighting the urgent need for new therapeutic alternatives. In this context, phenolic compounds such as octyl gallate (OG), an ester derivative of gallic acid, have shown promising antimicrobial and antiparasitic activity. This study aimed to evaluate the antileishmanial activity of OG against promastigote and axenic amastigote forms of L. donovani and L. infantum, as well as its cytotoxic profile in mammalian cells and its effects on parasite membrane integrity. Treatment of promastigote forms with different concentrations of OG resulted in significant parasite growth inhibition, with IC50 values of 2.61 μM for L. donovani and 2.79 μM for L. infantum. Against axenic amastigote forms of L. infantum, OG showed an IC50 of 15.6 μM, indicating relevant activity against this clinically significant stage. Cytotoxicity assays in LLC-MK2 and RAW 264.7 cells showed CC50 values of 417.2 μM and 349.8 μM, respectively, resulting in high selectivity indexes above 120, supporting the compound's safety toward host cells. Furthermore, membrane integrity assays using SYTOX Green revealed a significant increase in membrane permeability in L. infantum promastigotes, suggesting that OG’s mechanism of action may involve membrane destabilization. These findings indicate that OG exhibits a promising bioactive profile, combining antiparasitic efficacy, low cytotoxicity, and a possible membrane-targeting mechanism, making it a strong candidate for future studies in the development of new therapies for visceral leishmaniasis.