1. Evaluation of Biological Activities of Quinone-4-oxoquinoline Derivatives against Pathogens of Clinical Importance
- Author
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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, and Helena Carla Castro
- Subjects
Structure-Activity Relationship ,4-Quinolones ,Drug Discovery ,Gram-Negative Bacteria ,Quinones ,Humans ,General Medicine ,Microbial Sensitivity Tests ,Quinolones ,Gram-Positive Bacteria ,Anti-Bacterial Agents - Abstract
Background:Microbial resistance has become a worldwide public health problem, and may lead to morbidity and mortality in affected patients.Objective:Therefore, this work aimed to evaluate the antibacterial activity of quinone-4-oxoquinoline derivatives.Method:These derivatives were evaluated against Gram-positive and Gram-negative bacteria by their antibacterial activity, anti-biofilm, and hemolytic activities and by 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.
- Published
- 2021