Computational and preclinical prediction of the antimicrobial properties of an agent isolated from Monodora myristica: a novel DNA gyrase inhibitor

Onikanni, Sunday Amos and Lawal, Bashir and Fadaka, Adewale Oluwaseun and Bakare, Oluwafemi and Ezekiel, Adewole and Bakhtiar, Muhammad Taher and Khotib, Junaidi and Darnis, Deny Susanti and Oyinloye, Babatunji Emmanuel and Ajiboye, Basiru Olaitan and Ojo, Oluwafemi Adeleke and Sibuyi, Nicole Remaliah Samantha (2023) Computational and preclinical prediction of the antimicrobial properties of an agent isolated from Monodora myristica: a novel DNA gyrase inhibitor. Molecules, 28 (1953). pp. 1-16. ISSN 1420-3049

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Abstract

The African nutmeg (Monodora myristica) is a medically useful plant. We, herein, aimed to critically examine whether bioactive compounds identified in the extracted oil of Monodora myristica could act as antimicrobial agents. To this end, we employed the Schrödinger platform as the com- putational tool to screen bioactive compounds identified in the oil of Monodora myristica. Our lead compound displayed the highest potency when compared with levofloxacin based on its binding affinity. The hit molecule was further subjected to an Absorption, Distribution, Metabolism, Excre- tion (ADME) prediction, and a Molecular Dynamics (MD) simulation was carried out on molecules with PubChem IDs 529885 and 175002 and on three standards (levofloxacin, cephalexin, and novo- biocin). The MD analysis results demonstrated that two molecules are highly compact when com- pared to the native protein; thereby, this suggests that they could affect the protein on a structural and a functional level. The employed computational approach demonstrates that conformational changes occur in DNA gyrase after the binding of inhibitors; thereby, this resulted in structural and functional changes. These findings expand our knowledge on the inhibition of bacterial DNA gy- rase and could pave the way for the discovery of new drugs for the treatment of multi-resistant bacterial infections.

Item Type:	Article (Journal)
Uncontrolled Keywords:	Schrödinger; Monodora myristica; conformational; antibiotics; levofloxacin
Subjects:	Q Science > QD Chemistry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Pharmacy Kulliyyah of Pharmacy > Department of Pharmaceutical Technology Kulliyyah of Science Kulliyyah of Science > Department of Chemistry
Depositing User:	Dr Deny Susanti Darnis
Date Deposited:	08 Feb 2023 16:26
Last Modified:	17 Apr 2023 09:44
URI:	http://irep.iium.edu.my/id/eprint/103628

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