In silico molecular targets, docking, dynamics simulation and physiologically based pharmacokinetics modeling of oritavancin DOI Creative Commons
Toluwase Hezekiah Fatoki,

Tosin Christianah Balogun,

Adebayo Emmanuel Ojewuyi

и другие.

BMC Pharmacology and Toxicology, Год журнала: 2024, Номер 25(1)

Опубликована: Окт. 22, 2024

Oritavancin is a semi-synthetic lipoglycopeptide antibiotic primarily used to treat serious infections caused by Gram-positive bacteria. The aim of this study was elucidate possible molecular targets oritavancin in human and microbes relevance its mechanism action model pharmacokinetics for optimal dose selection clinical practice. Computational methods were which include target prediction, docking, dynamics simulation, physiological-based (PBPK) modeling. moderately soluble water did not permeate the blood-brain barrier. Seven identified humans. Molecular docking results showed highest binding affinity with PI3-kinase p110-gamma subunit (−10.34 kcal/mol), followed Acyl-CoA desaturase (−10.07 kcal/mol) Cytochrome P450 2C19 (−8.384 kcal/mol). PBPK modelling adult that infusion has lower peak concentrations (Cmax) compared bolus administration, 1200 mg yielded Cmax 16.559 mg/L, 800 11.258 200 over 3 days 7.526 mg/L. Notably, gave extended half-life (t1/2) all doses slightly higher clearance rates bolus, particularly doses. corroborated existing pharmacokinetic data, confirmed model's accuracy predictive capability. This comprehensive computational provided invaluable insights into pharmacological profile Oritavancin, aiding further development optimization use.

Язык: Английский

In-silico screening of bioactive compounds of Moringa oleifera as potential inhibitors targeting HIF-1α/VEGF/GLUT-1 pathway against Breast Cancer DOI

Neha Masarkar,

Maynak Pal, Mithun Roy

и другие.

Journal of Complementary and Integrative Medicine, Год журнала: 2024, Номер unknown

Опубликована: Июль 18, 2024

Abstract Objectives Breast cancer is among the most heterogeneous and aggressive diseases a foremost cause of death in women globally. Hypoxic activation HIF-1α breast cancers triggers transcription battery genes encoding proteins that facilitate tumor growth metastasis correlated with poor prognosis. Based on reported cytotoxic anti-cancer properties Moringa oleifera ( Mo ), this study explores inhibitory effect bioactive compounds from M. target HIF-1α, VEGF, GLUT-1 silico . Methods The X-ray crystallographic structures GLUT1 were sourced Protein Data Bank (PDB) docked 70 3D PubChem using AutoDock Vina, binding modes analyzed Discovery Studio. Five highest energies selected further drug-likeness, oral bioavailability, ADME, toxicity profiles SwissADME, ADMETSaR, ADMETlab 3.0 web server. Results Out screened compounds, top five best identified namely Apigenin, Ellagic Acid, Isorhamnetin, Luteolin, Myricetin each receptor. Molecular docking results indicated ligands interact strongly receptors through hydrogen bonds hydrophobic interactions. These showed favorable drug-like pharmacokinetic properties, possessed no substantial toxicity, fairly bioavailable. Conclusions suggested possess strong potential developing putative lead targeting are safe natural plant-based drugs against cancer.

Язык: Английский

Процитировано

2
In silico molecular targets, docking, dynamics simulation and physiologically based pharmacokinetics modeling of oritavancin DOI Creative Commons
Toluwase Hezekiah Fatoki,

Tosin Christianah Balogun,

Adebayo Emmanuel Ojewuyi

и другие.

BMC Pharmacology and Toxicology, Год журнала: 2024, Номер 25(1)

Опубликована: Окт. 22, 2024

Oritavancin is a semi-synthetic lipoglycopeptide antibiotic primarily used to treat serious infections caused by Gram-positive bacteria. The aim of this study was elucidate possible molecular targets oritavancin in human and microbes relevance its mechanism action model pharmacokinetics for optimal dose selection clinical practice. Computational methods were which include target prediction, docking, dynamics simulation, physiological-based (PBPK) modeling. moderately soluble water did not permeate the blood-brain barrier. Seven identified humans. Molecular docking results showed highest binding affinity with PI3-kinase p110-gamma subunit (−10.34 kcal/mol), followed Acyl-CoA desaturase (−10.07 kcal/mol) Cytochrome P450 2C19 (−8.384 kcal/mol). PBPK modelling adult that infusion has lower peak concentrations (Cmax) compared bolus administration, 1200 mg yielded Cmax 16.559 mg/L, 800 11.258 200 over 3 days 7.526 mg/L. Notably, gave extended half-life (t1/2) all doses slightly higher clearance rates bolus, particularly doses. corroborated existing pharmacokinetic data, confirmed model's accuracy predictive capability. This comprehensive computational provided invaluable insights into pharmacological profile Oritavancin, aiding further development optimization use.

Язык: Английский

Процитировано

2