Molecular docking and ADME profiles of β-carboline analogues as potential antibiotic agents targeting DNA gyrase
Antibiotic resistance remains a major human threat worldwide, owing to bacteria and fungi's ability to mutate over time, as well as a dramatic decline in the antibiotic pipeline. Plants can produce a variety of bioactive secondary metabolites and beneficial for future antibiotic discovery. He...
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| Main Authors: | , , , |
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| Format: | Proceeding Paper |
| Language: | English |
| Published: |
2023
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/104617/1/104617_Molecular%20docking.pdf http://irep.iium.edu.my/104617/ |
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| Summary: | Antibiotic resistance remains a major human threat worldwide, owing to bacteria and fungi's ability to
mutate over time, as well as a dramatic decline in the antibiotic pipeline. Plants can produce a variety of
bioactive secondary metabolites and beneficial for future antibiotic discovery. Herein, using in-silico
approaches, an in-house library of 20 β-carboline analogues was virtually screened to evaluate their
antibiotic activities and drug-likeness properties. The molecular docking using DNA gyrase crystal
structure (PDB ID: 1AJ6) showed that 19 derivatives bind strongly to the target protein (in a range of -
6.8 kcal/mol to -9.4 kcal/mol) except 1o (-6.7 kcal/mol) which exhibited comparable binding energy to
the reference drug, novobiocin (-6.8 kcal/mol). Of these, derivatives 1l bind strongest (-9.4 kcal/mol)
mainly due to the hydrogen bond interactions that occur between the carboxylic acid moiety and
secondary amine with Val71 and Asp73 residues, respectively. ADME profiling predicted that almost
all β-carboline analogues demonstrated favourable drug-likeness properties and bioavailability profiles,
suggesting their potential DNA gyrase inhibitors. Thus, through this work, the derivatives of β-carboline
may serve as a starting point for the development of effective antibacterial medications through further
modification and optimisation process. |
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