Scholarship 22/15005-7 - Modificação molecular, Mycobacterium tuberculosis - BV FAPESP
Advanced search
Start date
Betweenand

Synthesis and evaluation of new benzofuroxan derivatives designed to act against drug-resistant Mycobacterium tuberculosis

Grant number: 22/15005-7
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date until: March 01, 2023
End date until: February 29, 2024
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Jean Leandro dos Santos
Grantee:Any Caroline Xavier
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), which mainly affects the lungs, but also exists in the extrapulmonary form. In the last few years, TB treatment has advanced considerably; however many challenges, such as the emergence of resistant strains, have menaced the fulfillment of the goal of eliminating the disease by 2035, proposed by the World Health Organization (WHO). In 2018, approximately 10 million new cases of TB were estimated, of which 484,000 corresponded to infection by multidrug-resistant M. tuberculosis (MDR-TB) and to some degree by extensively drug-resistant strains (XDR-TB), according to WHO data. Intending to improve the scenario described above, several research groups have formed partnerships and invested much effort in discovering new, more effective, and safer drugs against Mtb. In our research group, one of the most active compounds discovered in years of study was BZ8, which was able to reset the colony-forming units in the lungs of animals to zero, in addition to presenting a high selectivity index and absence of cytotoxic, mutagenic and genotoxic. In subsequent studies to identify the mechanism of action of BZ8, it was discovered that this compound can interfere with protein synthesis in Mycobacterium. In view of the previously exposed points, this project seeks to synthesize and characterize new alpha-beta unsaturated ketones (chalcones) containing the N-oxide functions benzofuroxane and quinoxaline, obtained from computational molecular modifications of BZ8. The planned chalcones explore the optimization of BZ8 through bioisosterism to reduce its instability in an acid medium and seek new candidates against MDR-TB and XDR-TB. Analytical methods will do the characterization of the new compounds and the pharmacological evaluation will be conducted in 3 cell lines (MRC-5, Hep G2 and J774A.1), in the H37Rv strain and clinical isolates of MDR-TB and XDR-TB. Finally, the present study is expected to identify new drug candidates that, in addition to improving the current treatment, are also an alternative to the treatment of multidrug-resistant TB.

News published in Agência FAPESP Newsletter about the scholarship:
More itemsLess items
Articles published in other media outlets ( ):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)

Please report errors in scientific publications list using this form.