Evaluation of pharmacological interaction and bactericidal kinetics of new furoxanic molecules in combination with rifampicin, isoniazid, amikacin, and moxifloxacin against Mycobacterium tuberculosis H37Rv

• Grant number: 14/03920-6
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2014
• Effective date (End): July 31, 2015
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal researcher: Joás Lucas da Silva
• Grantee: Camila Maríngolo Ribeiro
• 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

Abstract

In this project, we propose to evaluate the pharmacological interactions and possible synergistic effects of rifampin, isoniazid, amikacin, moxifloxacin, and five new furoxanic molecules obtained by the synthesis in LAPDESF (Laboratory of Drug Research and Development)at FCFAR/UNESP, which demonstrated promising against Mycobacterium tuberculosis. This project is part of the Young Researcher Project (No. 2013/14957-5 ) recently awarded under the coordination of Prof.Dr. Rogério Fernando Pavan. The study of new drug combinations to combat Mycobacterium tuberculosis is important to add new drugs to treat tuberculosis and Evaluation of new molecules with potential activity against mycobacteria. Two methods that will be used to study the synergism of molecules are the checkerboard and bactericidal kinetics. The checkerboard method allows evaluating drug combinations that show synergism or not and which are the best synergistic concentrations for two or more molecules. However, with this method, we can not evaluate the synergistic effect over time. By doing the bactericidal kinetic assay it is possible to expose the Mycobacterium to different Combinations of drugs in different concentrations. Every 24 Hours An aliquot of the sample is taken, diluted, plated onto plates, and incubated for counting mycobacteria. Results are expressed in Colony Forming Units per milliliter (CFU/mL). with the data obtained, it is possible to construct a time-kill curve and thus observe the quantitative measure of the intensity of the bactericidal effect. (AU)

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)

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.