Molecular modeling, density functional theory, ADME prediction and antimicrobial activity studies of 2-(substituted)oxazolo[4,5-b]pyridine derivatives
Küçük Resim Yok
Tarih
2021
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Royal Soc Chemistry
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
In 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.
Açıklama
Anahtar Kelimeler
Homo-Lumo, Inhibitors, Mep, Dft, Benzimidazoles, Benzoxazoles, Mechanisms, Resistance, Dynamics, Docking
Kaynak
New Journal Of Chemistry
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
45
Sayı
25
