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Isolation and Antitrypanosomal Evaluation of Secondary Metabolites from the Marine Bacteria Bacillus altitudinis

Grant number: 23/07414-7
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): October 01, 2023
Effective date (End): February 28, 2025
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:André Gustavo Tempone Cardoso
Grantee:Mariana Babberg Abiuzi
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Comprising a vast chemodiversity, bacteria isolated from the marine microbiome have been gaining attention in the pharmaceutical field, providing unprecedented secondary metabolites as drug prototypes. Among the neglected diseases of great relevance to WHO is Chagas disease, which affects 8 million people worldwide. With only a single drug approved in Brazil with high therapeutic failure and severe adverse effects, there is an urgent need for research into new therapies. This project aims at the isolation of secondary metabolites of the marine bacteria Bacillus altitudinis, obtained from a seaweed. Bioactive compounds will be isolated by different chromatographic techniques, including high performance liquid chromatography. At the same time, nuclear magnetic resonance and high-resolution mass spectrometry will be used in order to dereplicate and structurally elucidate the active compounds. Pure compounds will be evaluated for potency in intracellular trypomastigotes and amastigotes, aiming to determine the 50% Effective Concentration. Cytotoxicity studies will be carried out in mammalian cells to determine the Selectivity Index, as well as the evaluation of hemolytic activity. Through the in silico SwissADME platform, analyzes will be carried out for the elimination of interfering compounds (PAINS) and evaluation of the "druglikeness" profile. The mechanism of action of the most promising compound will be evaluated in trypomastigotes to study: i) the plasma membrane permeability, ii) the plasma membrane potential (”Èp), iii) the mitochondrial membrane potential (”Èm), iv) the levels of ATP, and v) the protein profile by MALTI-TOF/MS. Thus, this project aims to contribute with future pharmaceutical prototypes for neglected diseases such as Chagas disease.

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