Docking and Molecular Dynamic of Microalgae Compounds as Potential Inhibitors of Beta-Lactamase

• Published in: International journal of molecular sciences 2022-01, Vol.23 (3), p.1630
• Main Authors: Pestana-Nobles, Roberto, Aranguren-Díaz, Yani, Machado-Sierra, Elwi, Yosa, Juvenal, Galan-Freyle, Nataly J, Sepulveda-Montaño, Laura X, Kuroda, Daniel G, Pacheco-Londoño, Leonardo C
• Format: Article
• Language: English
• Subjects: Acids; Algae; Amides; Antibacterial materials; Antibiotics; Aquatic microorganisms; Bacteria; Bacteria - drug effects; Bacteria - enzymology; Bacterial infections; beta-Lactam Resistance; beta-Lactamase Inhibitors - chemistry; beta-Lactamase Inhibitors - pharmacology; beta-Lactamases - chemistry; beta-Lactamases - metabolism; Biological Factors - chemistry; Biological Factors - pharmacology; Biosynthesis; Clavulanic acid; Clinical medicine; Computer applications; Depsipeptides - chemistry; Depsipeptides - pharmacology; docking; Drug resistance; Enzymes; Homology; Inhibitors; Medicine; Metabolites; microalgae; Microalgae - chemistry; Microorganisms; Models, Molecular; Molecular docking; Molecular Docking Simulation; molecular dynamic; Molecular dynamics; Molecular Dynamics Simulation; Molecular Structure; Mutation; Penicillin; Protein Conformation; Public health; Quercetin; Quercetin - chemistry; Quercetin - pharmacology; Sulbactam; Tazobactam; β Lactamase; β-Lactam antibiotics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031630

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 β-lactam antibiotics. The increasing resistance to those antibiotics by bacterial pathogens generated the emergence of extended-spectrum β-lactamases (ESBLs), an actual public health problem. This is due to rapid mutations of bacteria when exposed to antibiotics. In this case, β-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 β-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 β-lactamase. Six 3D β-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 β-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 β-lactamase inhibitors or as structural templates for new in-silico pharmaceutical designs, with the possibility of combatting β-lactam resistance.