Title:Synthesis and Biological Evaluation of Coumarins Derivatives as Potential Inhibitors of the Production of Pseudomonas aeruginosa Virulence Factor Pyocyanin
VOLUME: 18 ISSUE: 2
Author(s):Luana da S.M. Forezi, Thamires Quadros Froes, Mariana F.C. Cardoso, Carine Assuncao de Oliveira Maciel, Gianluca G. Nicastro, Regina L. Baldini, Dora C.S. Costa, Vitor F. Ferreira, Marcelo S. Castilho* and Fernando de C. da Silva*
Affiliation:Departamento de Quimica Organica, Universidade Federal Fluminense, Instituto de Quimica, Niteroi, RJ, 24020-150, Programa de pos-graduacao em Biotecnologia da Universidade Estadual de Feira de Santana, Feira de Santana, BA, Departamento de Quimica Organica, Universidade Federal Fluminense, Instituto de Quimica, Niteroi, RJ, 24020-150, Programa de pos-graduacao em Biotecnologia da Universidade Estadual de Feira de Santana, Feira de Santana, BA, Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo, Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo, Departamento de Quimica Organica, Universidade Federal Fluminense, Instituto de Quimica, Niteroi, RJ, 24020-150, Universidade Federal Fluminense, Departamento de Tecnologia Farmaceutica, Faculdade de Farmacia, Niteroi, RJ, 24241-002, Departamento de Quimica Organica, Universidade Federal Fluminense, Instituto de Quimica, Niteroi, RJ, 24020-150, Departamento de Quimica Organica, Universidade Federal Fluminense, Instituto de Quimica, Niteroi, RJ, 24020-150
Keywords:Antimicrobial resistance, anti-virulence, cellular assay, phenazine, 2H-chromen-2-one, inhibitor.
Abstract:Antimicrobial Resistance (AMR) is a serious problem for the humans since it threatens the
effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites,
viruses and fungi. One way around this problem is to act on the virulence factors, produced by
bacteria, which increase their infection effectiveness. In view of these facts, new coumarin derivatives
were synthesized and evaluated for their anti-virulence biological activity towards Pseudomonas
aeruginosa. The results suggest that coumarin derivatives with a secondary carbon at C-3 position
reduces P. aeruginosa growth whereas compounds with one additional substituent have a significant
effect over pyocyanin production (10k EC50 7 ± 2 µM; 10l EC50 42 ± 13 µM). Moreover, 10k reduces P.
aeruginosa motility and biofilm formation, what is compatible with a quorum sensing related mechanism
of action.
