Abordagem metabolômica aplicada em promastigotas de Leishmania amazonensis tratadas com mefloquina

Abstract

Leishmaniases comprise a group of diseases caused by protozoa of the genus Leishmania (Trypanosomatidae), which remain a serious public health problem, mainly affecting socially and economically vulnerable populations. Among the measures for disease control and reduction of incidence, chemotherapy represents an indispensable tool; however, it faces challenges due to the emergence of resistance of Leishmania spp. to the main drugs currently in use. In this context, metabolomics has been applied in parasitology to investigate the mechanisms of action of drugs used in leishmaniasis treatment, as well as in the search for new anti-Leishmania agents. In this study, we sought to investigate the potential of mefloquine, an antimalarial agent, against Leishmania amazonensis promastigotes through a global metabolomic approach. This approach employed separation techniques coupled with mass spectrometry as analytical platforms, specifically reversed-phase liquid chromatography–mass spectrometry (RPLC-MS) in both positive and negative ionization modes, and gas chromatography–mass spectrometry (GC-MS). After data processing, differentiation between the mefloquine-treated and untreated (control) groups was evaluated, as well as the discriminant metabolites between them, based on univariate and multivariate analyses. GC-MS analyses revealed higher levels of isoleucine, ribose/lyxose, and linoleic acid in the treated group. Meanwhile, RPLC-MS analyses indicated alterations mainly in metabolites belonging to glycerophospholipids, sphingolipids, fatty acids, amino acids, peptides, and analogs. Additionally, pathway analysis also demonstrated that the steroid biosynthesis pathway was affected during treatment. In this context, although preliminary, since the assays were performed against the promastigote form of the parasite, it can be inferred that mefloquine exhibits a multi-target mechanism of action in the death of L. amazonensis.