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Molecules ; 27(20)2022 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-36296585

RESUMEN

Multi-drug resistance is increasing in the pathogenic bacterium S. pneumoniae, which is mainly responsible for meningitis and community-acquired pneumonia (CAP), highlighting the need for new anti-pneumococcal agents. We have identified a potential anti-pneumococcal agent, enol 3, which acts by hindering the cell division process by perturbing Z-ring dynamics inside the cell. Enol 3 was also shown to inhibit FtsZ polymerization and induce its aggregation in vitro but does not affect the activity of tubulin and alkaline phosphatase. Docking studies show that 3 binds near the T7 loop, which is the catalytic site of FtsZ. Similar effects on Z-ring and FtsZ assembly were observed in B. subtilis, indicating that 3 could be a broad-spectrum anti-bacterial agent useful in targeting Gram-positive bacteria. In conclusion, compound 3 shows strong anti-pneumococcal activity, prompting further pre-clinical studies to explore its potential.


Asunto(s)
Proteínas Bacterianas , Proteínas del Citoesqueleto , Proteínas del Citoesqueleto/metabolismo , Proteínas Bacterianas/metabolismo , Tubulina (Proteína)/metabolismo , Fosfatasa Alcalina/metabolismo , Antibacterianos/farmacología , Antibacterianos/metabolismo , Bacillus subtilis
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