Search for the mechanism of action and therapeutic effect of new classes of drugs against Mycobacterium tuberculosis

• Grant number: 20/13497-4
• Support type: Regular Research Grants
• Duration: July 01, 2021 - June 30, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal researcher: Fernando Rogério Pavan
• Grantee: Fernando Rogério Pavan
• Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Assoc. researchers: Daniele Castagnolo ; Jean Leandro dos Santos

Abstract

Tuberculosis (TB) is one of the 10 leading causes of death in the world and is the disease caused by a single infectious agent with a higher mortality rate, being ahead of HIV/AIDS. Its complex and long treatment, added to the high rate of bacterial resistance makes it one of the targets pointed out by the World Health Organization along with 12 more bacteria as determinants in the urgency in research and development (R&D) of new antimicrobials. In the last 8 years, we researched different classes of new compounds with possible properties against Mycobacterium tuberculosis and found 7 highly promising compounds, which are: synthetic compounds and benzofuroxan derivatives BZ8, TB10 and TB13, natural compounds tanshinone I, tanshinone IIA and Cryptotanshinone and the complex commercial tris- (1,10-phenanthroline)iron(II). We can divide them into 3 groups, with completely different chemical characteristics, but with high potential within a pipeline to search for new drugs against TB. Alongside these compounds, we developed, together with a group from King's College, a nanocarrier (liposome) functionalized with siderophores and moxifloxacin. At the present moment of the research, we need to understand what is the therapeutic effect of these compounds in models of BALB/c mice and understand the mechanism of action of each one through the complete genomic sequencing (SGC) of naturally resistant mutants. The results obtained in this project, added to all previous studies, will lead to the final outcome of these compounds and the possibility of a new product to be presented to the pharmaceutical industry. (AU)