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Curr Top Med Chem ; 22(12): 973-991, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35524665

RESUMO

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.


Assuntos
Bactérias Gram-Negativas , Quinolonas , 4-Quinolonas , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias Gram-Positivas , Humanos , Testes de Sensibilidade Microbiana , Quinolonas/farmacologia , Quinonas/farmacologia , Relação Estrutura-Atividade
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