Title:Evaluation of Biological Activities of Quinone-4-oxoquinoline Derivatives
against Pathogens of Clinical Importance
Volume: 22
Issue: 12
Author(s): Francislene Juliana Martins, Fernanda Savacini Sagrillo, Rafaelle Josianne Vinturelle Medeiros, Alan Gonçalves de Souza, Amanda Rodrigues Pinto Costa, Juliana Silva Novais, Leonardo Alves Miceli, Vinícius Campos, Agnes Marie Sá Figueiredo, Anna Claudia Cunha, Natalia Lidmar von Ranke, Murilo Lamim Bello, Bárbara Abrahim-Vieira, Alessandra De Souza, Norman Ratcliffe, Fernanda da Costa Santos Boechat, Maria Cecília Bastos Vieira de Souza*, Carlos Rangel Rodrigues*Helena Carla Castro*
Affiliation:
- Department of Organic Chemistry, Chemistry Institute, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil
- Department of Drugs and Medicines, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- Institute of Biology, Postgraduate Program in Science and Biotechnology, Federal Fluminense University, Niterói,
Rio de Janeiro, Brazil
Keywords:
Drug resistance, Antibacterial agents, Quinone derivatives, 4-Oxoquinolines, Gram-positive bacterial infections, Gram-negative bacterial infections.
Abstract:
Background: Microbial resistance has become a worldwide public health problem and
may lead to morbidity and mortality in affected patients.
Objectives: Therefore, this work aimed to evaluate the antibacterial activity of quinone-4-
oxoquinoline derivatives.
Methods: These derivatives were evaluated against Gram-positive and Gram-negative bacteria by
their antibacterial activity, anti-biofilm, and hemolytic activities and in silico assays.
Results: The quinone-4-oxoquinoline derivatives presented broad-spectrum antibacterial activities
and, in some cases, were more active than commercially available reference drugs. These compounds
also inhibited bacterial adhesion, and the assays revealed seven non-hemolytic derivatives.
The derivatives seem to cause damage to the bacterial cell membrane, and those containing the carboxyl
group at the C-3 position of the 4-quinolonic nucleus were more active than those containing
a carboxyethyl group.
Conclusion: The isoquinoline-5,8-dione nucleus also favored antimicrobial activity. The study
showed that the target of the derivatives must be a non-conventional hydrophobic allosteric binding
pocket on the DNA gyrase enzyme.
