Analysis of in vitro, in vivo and mechanism of action of benzofuroxan compounds against Mycobacterium tuberculosis

• Grant number: 18/21778-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2019
• End date: September 30, 2022
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Fernando Rogério Pavan
• Grantee: Debora Leite Campos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

The high number of infections caused by resistant bacteria shows an urgency for new antimicrobials. For Tuberculosis, this situation is no different. Caused mainly by the bacillus Mycobacterium tuberculosis, this is the infectious disease that kills the most in the world and, in 2017, caused 1.3 million deaths. Because of that, this project aims at the in vitro and in vivo study and also the search of the mechanism of action of 17 new benzofuroxan compounds, synthesized through the technique of molecular hybridization. These compounds were developed based on the chemical structure of linezolid - known for its inhibitory effect against resistant and non-replicating bacteria - and of compound 8 - benzofuroxane derivative, which has activity against resistant and non-replicating intramacrophagous bacilli. These compounds, previously evaluated, presented excellent values of Minimum Inhibitory Concentration (MIC 90), and 11 of them presented MIC values below 5.0 mg/mL. Given this promising result, we will determine the selectivity index, evaluating its cytotoxic potential in vitro. In addition, we will evaluate its bactericidal or bacteriostatic action, its spectrum of activity and its capacity of inhibition against non-replicating and intramacrophagic bacilli. Finally, by selecting those that present the best results, we will proceed with the in vivo evaluation of anti-Mycobacterium tuberculosis action and toxicity in mice. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SOLCIA, MARIANA CRISTINA; CAMPOS, DEBORA LEITE; GRECCO, JULIA ARAUJO; PAIVA SILVA, CAIO SANDER; DA SILVA, PATRICIA BENTO; DA SILVA, ISABEL CRISTIANE; BALDUINO DA SILVA, ANA PAULA; SILVA, JOAS; ODA, FERNANDO BOMBARDA; DOS SANTOS, ANDRE GONZAGA; et al. rowth-inhibitory effects of tris-(1,10-phenanthroline) iron (II) against Mycobacterium tuberculosis in vitro and in viv. TUBERCULOSIS, v. 128, MAY 2021. (20/13497-4, 18/12270-6, 17/12419-7, 16/24633-0, 18/21778-3, 18/12135-1, 18/00163-0)

FERNANDES, GUILHERME F. S.; CAMPOS, DEBORA L.; DA SILVA, ISABEL C.; PRATES, JOAO L. B.; PAVAN, ALINE R.; PAVAN, FERNANDO R.; DOS SANTOS, JEAN L.. Benzofuroxan Derivatives as Potent Agents against Multidrug-Resistant Mycobacterium tuberculosis. CHEMMEDCHEM, v. 16, n. 8, FEB 2021. (18/00163-0, 18/17739-2, 18/21778-3, 18/24783-8, 18/11079-0, 16/09502-7)

SOLCIA, MARIANA CRISTINA; CAMPOS, DEBORA LEITE; GRECCO, JULIA ARAUJO; PAIVA SILVA, CAIO SANDER; DA SILVA, PATRICIA BENTO; DA SILVA, ISABEL CRISTIANE; BALDUINO DA SILVA, ANA PAULA; SILVA, JOAS; ODA, FERNANDO BOMBARDA; DOS SANTOS, ANDRE GONZAGA; et al. Growth-inhibitory effects of tris-(1,10-phenanthroline) iron (II) against Mycobacterium tuberculosis in vitro and in vivo. TUBERCULOSIS, v. 128, p. 8-pg., 2021-05-19. (18/00163-0, 16/24633-0, 18/21778-3, 17/12419-7, 18/12270-6, 18/12135-1, 20/13497-4)

CAMPOS, DEBORA LEITE; DEMARQUI, FERNANDA MANAIA; SOLCIA, MARIANA CRISTINA; DE SOUZA, PAULA CAROLINA; DA SILVA MAIA, PEDRO IVO; DEFLON, VICTOR MARCELO; PAVAN, FERNANDO ROGERIO. Latent Tuberculosis: A Promising New Compound to Treat Non-Replicating and Intramacrophagic Mycobacteria. BIOMEDICINES, v. 10, n. 10, p. 12-pg., 2022-10-01. (20/13497-4, 18/21778-3)