Computational and Preclinical Prediction of the Antimicrobial Properties of an Agent Isolated from <i>Monodora myristica</i>: A Novel DNA Gyrase Inhibitor
Sunday Amos Onikanni,
Bashir Lawal,
Adewale Oluwaseun Fadaka,
Oluwafemi Bakare,
Ezekiel Adewole,
Muhammad Taher,
Junaidi Khotib,
Deny Susanti,
Babatunji Emmanuel Oyinloye,
Basiru Olaitan Ajiboye,
Oluwafemi Adeleke Ojo,
Nicole Remaliah Samantha Sibuyi
Affiliations
Sunday Amos Onikanni
College of Medicine, Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan
Bashir Lawal
Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Adewale Oluwaseun Fadaka
Department of Biotechnology, University of the Western Cape, Bellville 7530, South Africa
Oluwafemi Bakare
Department of Biochemistry, Faculty of Science, Adekunle Ajasin University, Akungba Akoko 342111, Nigeria
Ezekiel Adewole
Industrial Chemistry Unit, Department of Chemical Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria
Muhammad Taher
Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Pahang, Malaysia
Junaidi Khotib
Department of Pharmacy Practice, Faculty of Pharmacy, Airlangga University, Surabaya 60115, Indonesia
Deny Susanti
Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia, Kuantan 25200, Pahang, Malaysia
Babatunji Emmanuel Oyinloye
Biochemistry Unit, Department of Chemical Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria
Basiru Olaitan Ajiboye
Institute of Drug Research and Development, SE Bogoro Center, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria
Oluwafemi Adeleke Ojo
Phytomedicine, Molecular Toxicology, and Computational Biochemistry Research Laboratory (PMTCB-RL), Department of Biochemistry, Bowen University, Iwo 232101, Nigeria
Nicole Remaliah Samantha Sibuyi
Department of Biotechnology, University of the Western Cape, Bellville 7530, South Africa
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 computational 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, Excretion (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 novobiocin). The MD analysis results demonstrated that two molecules are highly compact when compared 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 gyrase and could pave the way for the discovery of new drugs for the treatment of multi-resistant bacterial infections.
