Dados do Trabalho

Título

Potential of Marine Microbial Metabolites from Bacillus altitudinis against Trypanosoma cruzi: An in vitro Study

Introdução

Chagas disease affects about 8 million people, with only one drug available in Brazil.
Considering the therapeutic limitations of this protozoan disease, including several
adverse effects and a low efficacy, there is a need for new therapeutic options. The
marine environment has been a source of more than 20,000 inspirational natural
products discovered over the past 50 years. From these studies, 9 approved drugs have
been discovered, either as natural products or molecules inspired from the natural
scaffolds.

Objetivo (s)

Comprising a vast chemodiversity, marine microbial metabolites are promising
sources for new pharmaceutical prototypes with a broad range of biological activities
described. In this work, we isolated an endophyte bacteria from a marine algae and
studied the anti-Trypanosoma cruzi (Y strain) potential of the secondary metabolites.

Material e Métodos

The bacteria was characterized by MALDI-TOF/MS. The secondary metabolites were obtained using different solvents in liquid-liquid partition and were prefractionated in a reverse phase C18 solid-phase extraction cartridges and tested against the trypomastigotes at 150 µg/mL for 24h. Using Nuclear Magnetic Resonance (1H NMR) and HPLC-HRMS (HPLC-high resolution mass spectrometry), a fraction was selected as the most promising.

Resultados e Conclusão

The bacteria was characterized by MALDI-TOF/MS as a Bacillus altitudinis. The secondary metabolites were obtained using different solvents in liquid-liquid partition and were prefractionated in a reverse phase C18 solid-phase extraction cartridges, yielding four fractions (FI to FIV). When tested against the trypomastigotes at 150 µg/mL for 24h, FI
to FIV killed 100% of the parasites by the resazurin assay. Using Nuclear Magnetic Resonance (1H NMR) and HPLC-HRMS (HPLC-high resolution mass spectrometry), fraction FII was selected as the most promising, with the presence of fatty acids as well as an alkaloid with the formula C12H10NO. The fraction FII resulted in an 50% Effective Concentration of 33 µg/mL. Isolation and chemical characterization of the active compound is ongoing and future studies in intracellular amastigotes and mammalian cytotoxicity studies are planned.

Palavras-chave

Trypanosoma cruzi, therapy, marine bacteria, Chagas disease, bioactive compondo.

Agradecimentos

Support: FAPESP 2021/04464-8 and CNPq 405691/2021-1.