Isolation and evaluation of anti-Trypanosoma cruzi secondary metabolites from the Marine bacteria Bacillus altitudinis

• Grant number: 21/12827-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2022
• End date: November 30, 2022
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: André Gustavo Tempone Cardoso
• Grantee: Mariana Babberg Abiuzi
• Host Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Chagas disease affects about 8 million people, with only one drug approved in Brazil. Considering the therapeutic limitations of this protozoa, as well as the lack of interest from the private sector in investing in new therapies, there is a need for research into new drugs. Comprising a vast chemodiversity, marine microbial metabolites are one of the important sources of new anti-infective pharmaceutical prototypes. This project aims to isolate through biomonitored studies in Trypanosoma cruzi, secondary metabolites of the marine bacterium Bacillus altitudinis, obtained from a seaweed from the north coast of São Paulo. Bioactive compounds, isolated by different chromatographic techniques (HPLC), will be analyzed by nuclear magnetic resonance dereplication studies. The structural elucidation of active compounds will be performed by spectrometric and spectroscopic techniques, with mass spectrometry and nuclear magnetic resonance, respectively. The pure compounds will be evaluated for potency in trypomastigotes and intracellular amastigotes, aiming to determine the Effective Concentration 50%. Cytotoxicity will be evaluated in NCTC mammalian cells to determine the Selectivity Index of active compounds. Through the in silico SwissADME platform, analyzes will be performed to eliminate interfering compounds (PAINS). Thus, this project aims to contribute with future pharmaceutical prototypes for neglected diseases such as Chagas disease.(AU)