Research for new drugs against tuberculosis: laboratory improvement to perform pre-clinical trials

• Grant number: 11/11593-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2011
• End date: October 31, 2012
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Clarice Queico Fujimura Leite
• Grantee: Fernando Rogério Pavan
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Mycobacterium tuberculosis (MTB), agent of tuberculosis (TB), is responsible for the death of around 2-3 million people annually and a global economic toll of ~$12 billion each year. No new specific drug against (MTB) has been developed since 1960 and the emergence of MDR-TB and XDR-TB highlight the ineffectiveness of current treatment. It is hoped that the new drug against TB could: (i) reduce the duration of the treatment; (ii) be active against resistant strains; (iii) do not to interfere with the retrovirals and (iv) be active against latent bacilli cells. As approach to research new compounds against TB, pharmaceutical companies and research institutions have been employing target-based high-throughput assays (DNA, enzymes&) getting few promising results. Our group has been searching new drugs candidates through phenotypic assays where the whole bacterial cell is analyzed. The pipeline being developed by group is shown to be economical and rational. The effectiveness of biological assays implemented to date can be proven through numerous publications and two patents. In this project, the fellowship candidate, Mr. Fernando R. Pavan, intends to deploy new pre-clinicals biological assays and apply the developed pipeline of new drugs against TB targeting 100 unpublished complexes of transition elements synthesized from bio-directed study, with the possibility at the end to introduce new inorganic drugs against TB for clinical trial. (AU)

Scientific publications

(8)

(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)

OLIVEIRA, CAROLINA G.; MAIA, PEDRO IVO DA S.; SOUZA, PAULA C.; PAVAN, FERNANDO R.; LEITE, CLARICE Q. F.; VIANA, ROMMEL B.; BATISTA, ALZIR A.; NASCIMENTO, OTACIRO R.; DEFLON, VICTOR M.. Manganese(II) complexes with thiosemicarbazones as potential anti-Mycobacterium tuberculosis agents. Journal of Inorganic Biochemistry, v. 132, n. SI, p. 21-29, MAR 2014. (11/11593-7, 09/54011-8, 11/16380-1)

PAIVA, ISABELA L.; DE CARVALHO, GUSTAVO S. G.; DA SILVA, ADILSON D.; CORBI, PEDRO P.; BERGAMINI, FERNANDO R. G.; FORMIGA, ANDRE L. B.; DINIZ, RENATA; DO CARMO, WEBERTON R.; LEITE, CLARICE Q. F.; PAVAN, FERNANDO R.; et al. Silver(I) complexes with symmetrical Schiff bases: Synthesis, structural characterization, DFT studies and antimycobacterial assays. Polyhedron, v. 62, p. 104-109, OCT 7 2013. (11/11593-7, 09/06499-1, 12/08230-2)

POGGI, MARIANA; BARROSO, RAFAEL; COSTA-FILHO, ANTONIO JOSE; DE BARROS, HELOISA BARBOSA; PAVAN, FERNANDO; LEITE, CLARICE QUEICO; GAMBINO, DINORAH; HELVECIA TORRE, MARIA. New Isoniazid Complexes, Promising Agents Against Mycobacterium tuberculosis. Journal of the Mexican Chemical Society, v. 57, n. 3, p. 198-204, JUL-SEP 2013. (11/11593-7, 09/06499-1)

MONDELLI, MELINA; PAVAN, FERNANDO; DE SOUZA, PAULA C.; LEITE, CLARICE Q.; ELLENA, JAVIER; NASCIMENTO, OTACIRO R.; FACCHIN, GIANELLA; TORRE, MARIA H.. Study of a series of cobalt(II) sulfonamide complexes: Synthesis, spectroscopic characterization, and microbiological evaluation against M. tuberculosis. Crystal structure of [Co( sulfamethoxazole)(2)(H2O)(2)]center dot H2O. Journal of Molecular Structure, v. 1036, p. 180-187, MAR 27 2013. (11/11593-7, 09/06499-1)

MOREIRA, RAQUEL R. D.; MARTINS, GILMARCIO Z.; PIETRO, ROSEMEIRE C. L. R.; SATO, DAISY N.; PAVAN, FERNANDO R.; LEITE, SERGIO R. A.; VILEGAS, WAGNER; LEITE, CLARICE Q. F.. Paepalanthus spp: Antimycobacterial activity of extracts, methoxylated flavonoids and naphthopyranone fractions. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, v. 23, n. 2, p. 268-272, MAR-APR 2013. (11/11593-7, 08/10390-2)

OLIVEIRA, CAROLINA G.; MAIA, PEDRO IVO DA S.; SOUZA, PAULA C.; PAVAN, FERNANDO R.; LEITE, CLARICE Q. F.; VIANA, ROMMEL B.; BATISTA, ALZIR A.; NASCIMENTO, OTACIRO R.; DEFLON, VICTOR M.. Manganese(II) complexes with thiosemicarbazones as potential anti-Mycobacterium tuberculosis agents. Journal of Inorganic Biochemistry, v. 132, p. 9-pg., 2014-03-01. (11/11593-7, 09/54011-8, 11/16380-1)

PAVAN, FERNANDO R.; POELHSITZ, GUSTAVO V.; DA CUNHA, LUCAS V. P.; BARBOSA, MARILIA I. F.; LEITE, SERGIO R. A.; BATISTA, ALZIR A.; CHO, SANG H.; FRANZBLAU, SCOTT G.; DE CAMARGO, MARIANA S.; RESENDE, FLAVIA A.; et al. In Vitro and In Vivo Activities of Ruthenium(II) Phosphine/Diimine/Picolinate Complexes (SCAR) against Mycobacterium tuberculosis. PLoS One, v. 8, n. 5, MAY 28 2013. (11/11593-7, 09/06499-1)

DE PRINCE, KARINA ANDRADE; SORDI, RENATA; PAVAN, FERNANDO ROGERIO; BARRETO SANTOS, ADOLFO CARLOS; ARAUJO, ANGELA R.; LEITE, SERGIO R. A.; LEITE, CLARICE Q. F.. ANTI-MYCOBACTERIUM TUBERCULOSIS ACTIVITY OF FUNGUS PHOMOPSIS STIPATA. Brazilian Journal of Microbiology, v. 43, n. 1, p. 224-229, JAN-MAR 2012. (11/11593-7, 08/10390-2)