دورية أكاديمية
Abyssomicin W and neoabyssomicin B are potential inhibitors of New Delhi metallo-β-Lactamase-1 (NDM -1): A computational approach.
| العنوان: | Abyssomicin W and neoabyssomicin B are potential inhibitors of New Delhi metallo-β-Lactamase-1 (NDM -1): A computational approach. |
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| المؤلفون: | Alsultan, Abdulrahman1 (AUTHOR), Aatif, Mohammad2 (AUTHOR), Muteeb, Ghazala3 (AUTHOR) |
| المصدر: | Pharmacognosy Magazine. Oct-Dec2022, Vol. 18 Issue 80, p893-902. 10p. |
| مصطلحات موضوعية: | *MOLECULAR docking, *MOLECULAR dynamics, *LIGAND binding (Biochemistry), *PROTEIN-ligand interactions, *HYDROGEN bonding interactions, *MOLECULAR interactions, *BETA lactam antibiotics, *DRUG resistance in bacteria |
| مصطلحات جغرافية: | NEW Delhi (India) |
| مستخلص: | Background: Antibiotic resistance in bacteria mediated by New Delhi Metallo-β-lactamase (NDM) is a global threat to human health with an enormous economic burden. NDM can hydrolyze all the β-lactam core-containing antibiotics including carbapenems, which are regarded as last resort antibiotics. Materials and Methods: A library of Abyssomicins was virtually screened to identify novel non-β-lactam ring-containing inhibitors of NDM-1. Different computational approaches such as molecular modeling, virtual screening, molecular docking, molecular dynamics simulation, ADMET profiling, and free energy calculations were utilized for this purpose. Results: Virtual screening and ADMET profiling shortlisted Abyssomicin W and Neoabyssomicin B as the most promising candidate molecules. An in-depth analysis of protein-ligand interactions by molecular docking revealed that both ligands bind the active site of NDM-1. The identified inhibitors interacted with key catalytic residues as well as other residues around the active site of NDM-1. Hydrogen bonding and hydrophobic interactions played a significant role in stabilizing the protein-inhibitor complexes. The docking energy of NDM-1-Abyssomicin W, and NDM-1-Neoabyssomicin B complexes were − 9.6 kcal/mol and − 9.5 kcal/mol, respectively, which were higher than NDM-1-Methicillin (control) complex (−7.3 kcal/mol). Molecular dynamics simulation and free energy calculations by MM-PBSA also confirmed the stability of NDM-1-Abyssomicin W, and NDM-1-Neoabyssomicin B complexes. Conclusion: The findings of this study suggest that Abyssomicins serve as potential inhibitors of NDM-1. However, these results need to be validated in vitro and in vivo. This study may serve as a basis for further developing Abyssomicins as novel inhibitors of β-lactamases. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: | Academic Search Index |
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