Molecular docking and ADME profiles of β-carboline analogues as potential antibiotic agents targeting DNA gyrase

Abdul Aziz, Ahmad Amzar and Aminudin, Nurul Iman and Pungot, Noor Hidayah and Hamzah, Nurasyikin (2023) Molecular docking and ADME profiles of β-carboline analogues as potential antibiotic agents targeting DNA gyrase. In: 3rd IKMPB Online Symposium 2023, Online. (Unpublished)

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Abstract

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.

Item Type:	Conference or Workshop Item (Slide Presentation)
Uncontrolled Keywords:	β-carboline, DNA Gyrase, Antibiotic, Molecular Docking, ADME Profile
Subjects:	Q Science > QD Chemistry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Science Kulliyyah of Science > Department of Chemistry
Depositing User:	Dr Nurasyikin Hamzah
Date Deposited:	11 Oct 2023 15:27
Last Modified:	11 Oct 2023 15:27
URI:	http://irep.iium.edu.my/id/eprint/104617

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