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Int J Mol Sci ; 23(3)2022 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-35163569

RESUMEN

Bacterial resistance is responsible for a wide variety of health problems, both in children and adults. The persistence of symptoms and infections are mainly treated with ß-lactam antibiotics. The increasing resistance to those antibiotics by bacterial pathogens generated the emergence of extended-spectrum ß-lactamases (ESBLs), an actual public health problem. This is due to rapid mutations of bacteria when exposed to antibiotics. In this case, ß-lactamases are enzymes used by bacteria to hydrolyze the beta-lactam rings present in the antibiotics. Therefore, it was necessary to explore novel molecules as potential ß-lactamases inhibitors to find antibacterial compounds against infection caused by ESBLs. A computational methodology based on molecular docking and molecular dynamic simulations was used to find new microalgae metabolites inhibitors of ß-lactamase. Six 3D ß-lactamase proteins were selected, and the molecular docking revealed that the metabolites belonging to the same structural families, such as phenylacridine (4-Ph), quercetin (Qn), and cryptophycin (Cryp), exhibit a better binding score and binding energy than commercial clinical medicine ß-lactamase inhibitors, such as clavulanic acid, sulbactam, and tazobactam. These results indicate that 4-Ph, Qn, and Cryp molecules, homologous from microalgae metabolites, could be used, likely as novel ß-lactamase inhibitors or as structural templates for new in-silico pharmaceutical designs, with the possibility of combatting ß-lactam resistance.


Asunto(s)
Bacterias/enzimología , Factores Biológicos/farmacología , Microalgas/química , Inhibidores de beta-Lactamasas/farmacología , beta-Lactamasas/metabolismo , Bacterias/efectos de los fármacos , Factores Biológicos/química , Depsipéptidos/química , Depsipéptidos/farmacología , Modelos Moleculares , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Conformación Proteica , Quercetina/química , Quercetina/farmacología , Resistencia betalactámica , Inhibidores de beta-Lactamasas/química , beta-Lactamasas/química
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