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Studies in vitro and in vivo of furoxan compounds with potential application for the treatment of tuberculosis

Grant number: 14/11586-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2014
Effective date (End): March 31, 2017
Field of knowledge:Health Sciences - Pharmacy
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Fernando Rogério Pavan
Grantee:Paula Carolina de Souza
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated research grant:13/14957-5 - Research potential against tuberculosis of a new class of furoxan compounds and nanostructured compounds of the ruthenium(II) and copper (II), AP.JP
Associated scholarship(s):16/02860-5 - In vitro and in vivo studies of furoxan compounds: permeability, frequency of resistance, activity against resistance strains and in vivo efficacy, BE.EP.DR

Abstract

Tuberculosis (TB) is an infectious disease caused mainly by the pathogen Mycobacterium tuberculosis (MTB), and is demanding the development of new strategies for its control. The mortality rate of TB has fallen 45% since 1990 and the world is on track to achieve the global target of 50% reduction by 2015. This optimistic scenario is fulfilled in relation to the total number of cases, however a new problem arises: the resistance. A fact proven by the estimated 450,000 new cases of MDR-TB in 2012 and the report of XDR - TB in 92 countries. The search for new drugs aims to improve the condition of the patient's treatment. In view of this problem, in 2013 we launched the proposal grant "Young Researcher - FAPESP" which has just been approved (No. 2013/14957-5). The PhD scholarship requested here is a fundamental part of the project. This project aims to investigate new five furoxan promising compounds. In preliminary studies, we found that these compounds have a high selective toxicity against MTB with extremely high activity with MIC values lower than 1 µg/mL along with low cytotoxicity against two different cell lines (Vero and J774A.1) providing a high select index. On one hand, as one of the mechanisms of escaping immune response, MTB skillfully suppress the pathways involved in the production of nitric oxide (NO) by macrophages. On the other hand, this class of compounds is described in the literature as having the ability to donate NO assisting the pathway that is suppressed during the TB infection. This hypothesis is effectively investigated with the safety of these new molecules in order to propose to the end, new molecules for the treatment of particular cases of TB resistance. (AU)

News published in Agência FAPESP Newsletter about the scholarship:

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)
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.; COSTA, C. A. S.; CHO, S. H.; WANG, Y.; FRANZBLAU, S. G.; DOS SANTOS, J. L.; PAVAN, F. R. Furoxan derivatives demonstrated in vivo efficacy by reducing Mycobacterium tuberculosis to undetectable levels in a mouse model of infection. BIOMEDICINE & PHARMACOTHERAPY, v. 130, OCT 2020. Web of Science Citations: 0.
DOS SANTOS FERNANDES, GUILHERME FELIPE; DE SOUZA, PAULA CAROLINA; MORENO-VIGURI, ELSA; SANTIVANEZ-VELIZ, MERY; PAUCAR, ROCIO; PEREZ-SILANES, SILVIA; CHEGAEV, KONSTANTIN; GUGLIELMO, STEFANO; LAZZARATO, LORETTA; FRUTTERO, ROBERTA; CHIN, CHUNG MAN; DA SILVA, PATRICIA BENTO; CHORILLI, MARLUS; SOLCIA, MARIANA CRISTINA; RIBEIRO, CAMILA MARINGOLO; PAIVA SILVA, CAIO SANDER; MARINO, LEONARDO BIANCOLINO; BOSQUESI, PRISCILA LONGHIN; HUNT, DEBBIE M.; DE CARVALHO, LUIZ PEDRO S.; DE SOUZA COSTA, CARLOS ALBERTO; CHO, SANG HYUN; WANG, YUEHONG; FRANZBLAU, SCOTT GARY; PAVAN, FERNANDO ROGERIO; DOS SANTOS, JEAN LEANDRO. Design, Synthesis, and Characterization of N-Oxide-Containing Heterocycles with in Vivo Sterilizing Antitubercular Activity. Journal of Medicinal Chemistry, v. 60, n. 20, p. 8647-8660, OCT 26 2017. Web of Science Citations: 10.
DOS SANTOS FERNANDES, GUILHERME FELIPE; DE SOUZA, PAULA CAROLINA; MARINO, LEONARDO BIANCOLINO; CHEGAEV, KONSTANTIN; GUGLIELMO, STEFANO; LAZZARATO, LORETTA; FRUTTERO, ROBERTA; CHUNG, MAN CHIN; PAVAN, FERNANDO ROGERIO; DOS SANTOS, JEAN LEANDRO. Synthesis and biological activity of furoxan derivatives against Mycobacterium tuberculosis. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 123, p. 523-531, NOV 10 2016. Web of Science Citations: 22.
DE SOUZA, PAULA C.; MAIA, PEDRO I. S.; DE BARROS, HELOISA B.; LEITE, CLARICE Q. F.; DEFLON, VICTOR M.; PAVAN, FERNANDO R. Vanadium Complexes with Hydrazone or Thiosemicarbazone Ligands as Potential Anti-Mycobacterium tuberculosis Agents. CURRENT CLINICAL PHARMACOLOGY, v. 10, n. 1, p. 66-72, 2015. Web of Science Citations: 1.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SOUZA, Paula Carolina de. Estudos in vitro e in vivo de compostos furoxânicos, benzofuroxânicos e quinoxalinas com potencial aplicação para o tratamento da tuberculose. 2017. 111 f. Doctoral Thesis - Universidade Estadual Paulista "Júlio de Mesquita Filho" Faculdade de Ciências Farmacêuticas..

Please report errors in scientific publications list by writing to: cdi@fapesp.br.