Molecular modeling, density functional theory, ADME prediction and antimicrobial activity studies of 2-(substituted)oxazolo[4,5-b]pyridine derivatives

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dc.authoridcelik, ismail/0000-0002-8146-1663
dc.authoridCelik, Ismail/0000-0002-8146-1663
dc.authoridKuyucuklu, Gulcan/0000-0003-1596-1659
dc.authorwosidcelik, ismail/AAX-3221-2020
dc.authorwosidCelik, Ismail/ABE-5813-2021
dc.contributor.authorCelik, Ismail
dc.contributor.authorErol, Meryem
dc.contributor.authorKuyucuklu, Gulcan
dc.date.accessioned2024-06-12T11:19:03Z
dc.date.available2024-06-12T11:19:03Z
dc.date.issued2021
dc.departmentTrakya Üniversitesien_US
dc.description.abstractIn this study, the antimicrobial activities of previously synthesized 2-(substituted)oxazolo[4,5-b]pyridine derivatives toward six bacteria strains and twelve related drug-resistant isolates, and one fungus strain and two related drug-resistant isolates were investigated via the microdilution method. P6 (2-(4-trifluoromethylphenyl)oxazolo[4,5-b]pyridine) and P7 (2-(4-trifluoromethoxyphenyl)oxazolo[4,5-b]pyridine) showed better activity against E. faecalis isolate and E. coli isolate than ampicillin with a MIC of 16 mu g mL(-1). In addition, P5 (2-(4-methoxyphenyl)oxazolo[4,5-b]pyridine) and P6 showed gentamicin-equivalent activity against P. aeruginosa, with a MIC of 16 mu g mL(-1), while P7 showed better activity than gentamicin, with a MIC of 8 mu g mL(-1). The compounds generally showed good to strong antimicrobial activities. Molecular docking and molecular dynamics simulations of the compounds were performed using the DNA gyrase enzyme, and the interactions were evaluated. The compounds showed an overlap at the DNA gyrase ATP binding site with similar protein-ligand interactions. Average RMSD values of the apo form, and P5-4KTN, P6-4KTN and P7-4KTN holo forms were measured to be 0.149 nm, 0.152 nm, 0.165 nm, and 0.146 nm, respectively. The P7 ligand stabilized the protein via further increasing its stability. HOMO-LUMO orbital energies and other electronic parameters derived from these energies, MEP and NBO analysis, and geometric optimization were obtained using DFT/B3LYP theory and the 6-311G(d,p) basis set. The LUMO-HOMO Delta E values for the most active compounds, P5, P6 and P7, are 4.3508, 4.4471, and 4.4852 eV, respectively. The predicted ADME profiles of the compounds were calculated, and they were compliant with Lipinski and other restrictive rules.en_US
dc.identifier.doi10.1039/d1nj00701g
dc.identifier.endpage11118en_US
dc.identifier.issn1144-0546
dc.identifier.issn1369-9261
dc.identifier.issue25en_US
dc.identifier.scopus2-s2.0-85109041022en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage11108en_US
dc.identifier.urihttps://doi.org/10.1039/d1nj00701g
dc.identifier.urihttps://hdl.handle.net/20.500.14551/25063
dc.identifier.volume45en_US
dc.identifier.wosWOS:000658408500001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherRoyal Soc Chemistryen_US
dc.relation.ispartofNew Journal Of Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectHomo-Lumoen_US
dc.subjectInhibitorsen_US
dc.subjectMepen_US
dc.subjectDften_US
dc.subjectBenzimidazolesen_US
dc.subjectBenzoxazolesen_US
dc.subjectMechanismsen_US
dc.subjectResistanceen_US
dc.subjectDynamicsen_US
dc.subjectDockingen_US
dc.titleMolecular modeling, density functional theory, ADME prediction and antimicrobial activity studies of 2-(substituted)oxazolo[4,5-b]pyridine derivativesen_US
dc.typeArticleen_US

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