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

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(4), С. 529 - 529

Опубликована: Апрель 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.

Язык: Английский

Tinospora cordifolia bioactive compounds as a novel sterol 14a-demethylase (CYP51) inhibitor: an in silico study DOI

Kolawole T. Mesileya,

Precious C. Onyeka,

Iyidola M. Adaramola

и другие.

In Silico Pharmacology, Год журнала: 2025, Номер 13(1)

Опубликована: Фев. 13, 2025

Язык: Английский

Процитировано

0
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

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(4), С. 529 - 529

Опубликована: Апрель 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.

Язык: Английский

Процитировано

0