Uvarinol and Dichamanetin Derived from Uvaria chamae as Potential Dual-Site Inhibitors Against PBP2a in Methicillin Resistant Staphylococcus aureus: An In Silico Study DOI Creative Commons
Emmanuel Ayodeji Agbebi, Shalom Oluwafunke Adeyemi, Adetola Ibukunoluwa Adewale

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 529 - 529

Published: April 4, 2025

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the resistant pathogenic microorganisms that poses a global health threat due to its resistance β-lactam antibiotics where protein penicillin-binding 2a (PBP2a) plays crucial role in resistance. This study explores potential phytochemicals from Uvaria chamae, plant with known medicinal properties, serve as dual-site inhibitors PBP2a, targeting both active and allosteric sites. Methods: Phytochemicals previously identified U. chamae were subjected molecular docking dynamics simulations evaluate their binding affinities stability at PBP2a’s The compounds’ pharmacokinetic profiles predicted silico using SwissADME tools. Root-mean-square deviation (RMSD), radius gyration, free energy analyzed for dynamic stability. Results: Among evaluated compounds, Uvarinol Dichamanetin demonstrated high compared co-crystallized ligand standard like ceftaroline. exhibited highest affinity sites, score −14.94 kcal/mol inhibition constant (Ki) 0.01 nM. Molecular further confirmed robust Dichamanetin, indicated by consistently lower RMSD values relative ligand. Pharmacokinetic predictions revealed favorable drug-likeness low toxicity, although showed limited gastrointestinal absorption. Conclusions: show promise PBP2a inhibitors, offering novel strategy combat MRSA Their structural properties make them viable candidates development, though experimental validation formulation optimization are necessary overcome bioavailability challenges.

Language: Английский

Uvarinol and Dichamanetin Derived from Uvaria chamae as Potential Dual-Site Inhibitors Against PBP2a in Methicillin Resistant Staphylococcus aureus: An In Silico Study DOI Creative Commons
Emmanuel Ayodeji Agbebi, Shalom Oluwafunke Adeyemi, Adetola Ibukunoluwa Adewale

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 529 - 529

Published: April 4, 2025

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the resistant pathogenic microorganisms that poses a global health threat due to its resistance β-lactam antibiotics where protein penicillin-binding 2a (PBP2a) plays crucial role in resistance. This study explores potential phytochemicals from Uvaria chamae, plant with known medicinal properties, serve as dual-site inhibitors PBP2a, targeting both active and allosteric sites. Methods: Phytochemicals previously identified U. chamae were subjected molecular docking dynamics simulations evaluate their binding affinities stability at PBP2a’s The compounds’ pharmacokinetic profiles predicted silico using SwissADME tools. Root-mean-square deviation (RMSD), radius gyration, free energy analyzed for dynamic stability. Results: Among evaluated compounds, Uvarinol Dichamanetin demonstrated high compared co-crystallized ligand standard like ceftaroline. exhibited highest affinity sites, score −14.94 kcal/mol inhibition constant (Ki) 0.01 nM. Molecular further confirmed robust Dichamanetin, indicated by consistently lower RMSD values relative ligand. Pharmacokinetic predictions revealed favorable drug-likeness low toxicity, although showed limited gastrointestinal absorption. Conclusions: show promise PBP2a inhibitors, offering novel strategy combat MRSA Their structural properties make them viable candidates development, though experimental validation formulation optimization are necessary overcome bioavailability challenges.

Language: Английский

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