Scholarship 16/24633-0 - Mycobacterium tuberculosis - BV FAPESP
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Study of the biological profile of tris-(1,10-phenanthroline) iron (II) complex and possible mechanisms of action against Mycobacterium tuberculosis

Grant number: 16/24633-0
Support Opportunities:Scholarships in Brazil - Master
Start date until: September 01, 2017
End date until: August 31, 2018
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Fernando Rogério Pavan
Grantee:Mariana Cristina Solcia
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Tuberculosis (TB) is an infectious disease and its principal causative agent is Mycobacterium tuberculosis. Although the disease has received advances that promote its control and treatment, TB is still responsible for about two million deaths annually, a rate higher than HIV. The high rates of disease occurrence are attributed in part to the emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) bacteria. Another contributing factor to this problem is the fact that approximately one-third of the population is infected with M. tuberculosis and about 10% of these cases will develop clinical manifestations, especially when co-infected with HIV. In view of the various research strategies, "repurposing" will be our strategy, studying the metal complex tris-(1,10-phenanthroline) iron (II) ([Fe(phen)3]2+). The phenanthroline (phen) binder has been extensively studied for decades because it is chemically versatile, exhibiting a satisfatory combination of structural and chemical properties. Phen is widely used because it has high binding capacity with different types of metals, and [Fe(phen)3]2+ as a precursor to a series of chemical reactions. However, it has been observed that both are able to disrupt the functioning of a wide variety of biological systems besides being easy to obtain and low cost. Our objective in this project will be to study new applications to this complex as a potential therapeutic agent against M. tuberculosis, contributing to the research of new drugs that are effective and easily accessible for the treatment of tuberculosis. Therefore, the activity of this complex will be determined against sensitive and resistant strains in intracellular bacteria and also in bacilli that are in the latency state. The study will also investigate possible mechanisms of action, through methodologies that allow the isolation and genomic sequencing of spontaneously resistant mutants, In addition to assessing if the complex may act by interfering with cell wall synthesis or protein synthesis of mycobacteria, through thin layer chromatography assays and the use of mycobacteriophages, as well as to analyze if this complex has the capacity to inhibit efflux pumps, by evaluating the accumulation of ethidium bromide in mycobacteria. (AU)

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Scientific publications
(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, . (20/13497-4, 18/12270-6, 17/12419-7, 16/24633-0, 18/21778-3, 18/12135-1, 18/00163-0)
DE SOUZA, P. C.; FERNANDES, G. F. S.; MARINO, L. B.; RIBEIRO, C. M.; DA SILVA, P. B.; CHORILLI, M.; SILVA, C. S. P.; RESENDE, F. A.; SOLCIA, M. C.; DE GRANDIS, R. A.; et al. Furoxan derivatives demonstrated in vivo efficacy by reducing Mycobacterium tuberculosis to undetectable levels in a mouse model of infection. BIOMEDICINE & PHARMACOTHERAPY, v. 130, . (18/11079-0, 18/00163-0, 14/03920-6, 17/12419-7, 16/09502-7, 14/02240-1, 13/14957-5, 16/02860-5, 14/24811-0, 16/24633-0, 18/17739-2, 15/19531-1, 16/22429-7, 14/11586-9)
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., . (18/00163-0, 16/24633-0, 18/21778-3, 17/12419-7, 18/12270-6, 18/12135-1, 20/13497-4)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SOLCIA, Mariana Cristina. Study of the biological profile of the tris-(1,10-phenanthroline)iron(II) complex and mechanisms of action against Mycobacterium tuberculosis. 2018. Master's Dissertation - Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara Araraquara.

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