Evaluation of Biological Activities of Quinone-4-oxoquinoline Derivatives against Pathogens of Clinical Importance

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.

Keywords: 4-Oxoquinolines; Antibacterial agents; Drug resistance; Gram-negative bacterial infections; Gram-positive bacterial infections; Quinone derivatives.