{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:29:00Z","timestamp":1789140540954,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Culture, Research and Technology of the Republic of Indonesia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 Schr\u00f6dinger 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.<\/jats:p>","DOI":"10.3390\/molecules28041593","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T01:32:05Z","timestamp":1675819925000},"page":"1593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Computational and Preclinical Prediction of the Antimicrobial Properties of an Agent Isolated from Monodora myristica: A Novel DNA Gyrase Inhibitor"],"prefix":"10.3390","volume":"28","author":[{"given":"Sunday Amos","family":"Onikanni","sequence":"first","affiliation":[{"name":"College of Medicine, Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan"},{"name":"Biochemistry Unit, Department of Chemical Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0676-5875","authenticated-orcid":false,"given":"Bashir","family":"Lawal","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3952-2098","authenticated-orcid":false,"given":"Adewale Oluwaseun","family":"Fadaka","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, University of the Western Cape, Bellville 7530, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0175-7980","authenticated-orcid":false,"given":"Oluwafemi","family":"Bakare","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, Adekunle Ajasin University, Akungba Akoko 342111, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8230-3325","authenticated-orcid":false,"given":"Ezekiel","family":"Adewole","sequence":"additional","affiliation":[{"name":"Industrial Chemistry Unit, Department of Chemical Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1463-3090","authenticated-orcid":false,"given":"Muhammad","family":"Taher","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Pahang, Malaysia"},{"name":"Pharmaceutics and Translational Research Group, Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Pahang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junaidi","family":"Khotib","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, Airlangga University, Surabaya 60115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5345-1150","authenticated-orcid":false,"given":"Deny","family":"Susanti","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia, Kuantan 25200, Pahang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2165-7936","authenticated-orcid":false,"given":"Babatunji Emmanuel","family":"Oyinloye","sequence":"additional","affiliation":[{"name":"Biochemistry Unit, Department of Chemical Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria"},{"name":"Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, Kwadlangezwa 3886, South Africa"},{"name":"Institute of Drug Research and Development, SE Bogoro Center, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basiru Olaitan","family":"Ajiboye","sequence":"additional","affiliation":[{"name":"Institute of Drug Research and Development, SE Bogoro Center, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria"},{"name":"Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, Oye-Ekiti 371104, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9331-396X","authenticated-orcid":false,"given":"Oluwafemi Adeleke","family":"Ojo","sequence":"additional","affiliation":[{"name":"Phytomedicine, Molecular Toxicology, and Computational Biochemistry Research Laboratory (PMTCB-RL), Department of Biochemistry, Bowen University, Iwo 232101, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7175-5388","authenticated-orcid":false,"given":"Nicole Remaliah Samantha","family":"Sibuyi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, University of the Western Cape, Bellville 7530, South Africa"},{"name":"Health Platform, Advanced Materials Division, Mintek, Randburg 2194, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"882","DOI":"10.3389\/fmicb.2016.00882","article-title":"The developing world urgently needs phages to combat pathogenic bacteria","volume":"7","author":"Nagel","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"De Kraker, M.E., Stewardson, A.J., and Harbarth, S. (2016). Will 10 million people die a year due to antimicrobial resistance by 2050?. PLoS Med., 13.","DOI":"10.1371\/journal.pmed.1002184"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/j.1751-7915.2008.00063.x","article-title":"Mechanism of action of and resistance to quinolones","volume":"2","author":"Madurga","year":"2009","journal-title":"Microb. Biotechnol."},{"key":"ref_4","first-page":"377","article-title":"DNA gyrase, topoisomerase IV, and the 4-quinolones","volume":"61","author":"Drlica","year":"1997","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15022","DOI":"10.1021\/bi048457z","article-title":"Assembly of dimeric variants of coumermycins by tandem action of the four biosynthetic enzymes CouL, CouM, CouP, and NovN","volume":"43","author":"Heide","year":"2004","journal-title":"Biochemistry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1042\/bst0270048","article-title":"DNA gyrase as a drug target","volume":"27","author":"Maxwell","year":"1999","journal-title":"Biochem. Soc. Trans."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1038\/42294","article-title":"Crystal structure of the breakage\u2013reunion domain of DNA gyrase","volume":"388","author":"Cabral","year":"1997","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nrd2201","article-title":"Drugs for bad bugs: Confronting the challenges of antibacterial discovery","volume":"6","author":"Payne","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/nature09197","article-title":"Type IIA topoisomerase inhibition by a new class of antibacterial agents","volume":"466","author":"Bax","year":"2010","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.1128\/AAC.00496-08","article-title":"Mechanism of action of the antibiotic NXL101, a novel nonfluoroquinolone inhibitor of bacterial type II topoisomerases","volume":"52","author":"Black","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_11","first-page":"390","article-title":"Antibacterial drug discovery in the age of resistance new technologies and partnerships are helping to meet the challenges of antibacterial R&D","volume":"5","author":"Benowitz","year":"2010","journal-title":"Microbe"},{"key":"ref_12","first-page":"1","article-title":"Phytochemical, antimicrobial and Gc-Ms of African nutmeg (Monodora Myristica)","volume":"2","author":"Adewole","year":"2013","journal-title":"Phytochem. Antimicrob. Gc-Ms Afr. Nutmeg."},{"key":"ref_13","unstructured":"Christophersen, C., and Larsen, C. (1991). Traditional Medicine: A Potential Resource: Exploitation of Natural Products, HC \u00d8rsted Institute."},{"key":"ref_14","unstructured":"Malaria, R.B. (2005). World Malaria Report 2005, UNICEF."},{"key":"ref_15","first-page":"355","article-title":"Medicinal plants and primary health care: An agenda for action","volume":"59","author":"Akerele","year":"1988","journal-title":"Fitoterapia"},{"key":"ref_16","first-page":"2","article-title":"Some physical properties of African nutmeg [Monodora myristica]","volume":"21","author":"Burubai","year":"2007","journal-title":"Int. Agrophys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0378-1127(76)90028-1","article-title":"Development of forest tree crops for food supplies in Nigeria","volume":"1","author":"Okafor","year":"1976","journal-title":"Forest Ecol. Manag."},{"key":"ref_18","unstructured":"Iwu, M.M. (1993). African Medicinal Plants, CRC Press."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1053\/rmed.2003.1432","article-title":"Anti-inflammatory activity of 1.8-cineol (eucalyptol) in bronchial asthma: A double-blind placebo-controlled trial","volume":"97","author":"Juergens","year":"2003","journal-title":"Respir. Med."},{"key":"ref_20","first-page":"508","article-title":"Inhibition of cytokine production and arachidonic acid metabolism by eucalyptol (1.8-cineole) in human blood monocytes in vitro","volume":"3","author":"Juergens","year":"1998","journal-title":"Eur. J. Med. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Alcoba, G., Ochoa, C., Babo Martins, S., Ruiz de Casta\u00f1eda, R., Bolon, I., Wanda, F., Comte, E., Subedi, M., Shah, B., and Ghimire, A. (2021). Novel transdisciplinary methodology for cross-sectional analysis of snakebite epidemiology at national scale. PLoS Negl. Trop Dis., 15.","DOI":"10.1371\/journal.pntd.0009023"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bakare, O.O., Fadaka, A.O., Akanbi, M.O., Akinyede, K.A., Klein, A., and Keyster, M. (2021). Evaluation of selected carotenoids of Lycopersicon esculentum variants as therapeutic targets for \u2018Alzheimer\u2019s disease: An in silico approach. BMC Mol. Cell. Biol., 22.","DOI":"10.1186\/s12860-021-00386-2"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1080\/07391102.2020.1847197","article-title":"Inhibitory potential of repurposed drugs against the SARS-CoV-2 main protease: A computational-aided approach","volume":"40","author":"Fadaka","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"119393","DOI":"10.1016\/j.molliq.2022.119393","article-title":"Computational prediction of potential drug-like compounds from Cannabis sativa leaf extracts targeted towards Alzheimer therapy","volume":"360","author":"Fadaka","year":"2022","journal-title":"J. Mol. Liq."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1080\/07391102.2020.1819880","article-title":"Computational insight of dexamethasone against potential targets of SARS-CoV-2","volume":"40","author":"Fadaka","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1080\/07391102.2020.1819425","article-title":"Deciphering the interaction of puerarin with cancer macromolecules: An in silico investigation","volume":"40","author":"Ojo","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fadaka, A.O., Sibuyi, N.R.S., Martin, D.R., Klein, A., Madiehe, A., and Meyer, M. (2021). Development of effective therapeutic molecule from natural sources against coronavirus protease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179431"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"37896","DOI":"10.1021\/acsomega.2c05061","article-title":"Computational target-based screening of anti-MRSA natural products reveals potential multitarget mechanisms of action through peptidoglycan synthesis proteins","volume":"7","author":"Oselusi","year":"2022","journal-title":"ACS Omega"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1080\/07391102.2020.1850363","article-title":"In silico inhibition of SGTP4 as a therapeutic target for the treatment of schistosomiasis","volume":"40","author":"Adekiya","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1021\/acs.jmedchem.6b01439","article-title":"Pharmacophore-based repositioning of approved drugs as novel Staphylococcus aureus NorA efflux pump inhibitors","volume":"60","author":"Astolfi","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Simoben, C.V., Robaa, D., Chakrabarti, A., Schmidtkunz, K., Marek, M., Lancelot, J., Kannan, S., Melesina, J., Shaik, T.B., and Pierce, R.J. (2018). A novel class of Schistosoma mansoni histone deacetylase 8 (HDAC8) inhibitors identified by structure-based virtual screening and in vitro testing. Molecules, 23.","DOI":"10.3390\/molecules23030566"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1021\/ct100578z","article-title":"PROPKA3: Consistent treatment of internal and surface residues in empirical p K a predictions","volume":"7","author":"Olsson","year":"2011","journal-title":"J. Chem. Theor. Comput."},{"key":"ref_33","unstructured":"Release, S. (2018). 2: QikProp, Schr\u00f6dinger, LLC."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jphs.2021.05.004","article-title":"Computational study of the therapeutic potentials of a new series of imidazole derivatives against SARS-CoV-2","volume":"147","author":"Johnson","year":"2021","journal-title":"J. Pharmacol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ymeth.2015.04.021","article-title":"Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecules based inhibitors against metallothionein-III to study Alzheimer\u2019s disease","volume":"83","author":"Roy","year":"2015","journal-title":"Methods"},{"key":"ref_36","first-page":"44","article-title":"Identification of potential inhibitors against acetylcholinesterase associated with Alzheimer's diseases: A molecular docking approach","volume":"1","author":"Sharma","year":"2011","journal-title":"J. Comput. Methods Mol. Des."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.biopha.2015.02.009","article-title":"Homology modelling and molecular docking of MDR1 with chemotherapeutic agents in non-small cell lung cancer","volume":"71","author":"Subhani","year":"2015","journal-title":"Biomed. Pharmacother."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Doron, S., and Gorbach, S. (2008). Bacterial infections: Overview. Int. Encyclopedia Public Health, 273\u2013282.","DOI":"10.1016\/B978-012373960-5.00596-7"},{"key":"ref_39","unstructured":"WHO (2019). 2019 Antibacterial Agents in Clinical Development: An Analysis of the Antibacterial Clinical Development Pipeline, WHO."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.compbiolchem.2018.04.002","article-title":"Targeting natural compounds against HER2 kinase domain as potential anticancer drugs applying pharmacophore based molecular modelling approaches","volume":"74","author":"Rampogu","year":"2018","journal-title":"Comput. Biol. Chem."},{"key":"ref_41","first-page":"82","article-title":"Poor aqueous solubility\u2014An industry wide problem in drug discovery","volume":"5","author":"Lipinski","year":"2002","journal-title":"Am. Pharm. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4601","DOI":"10.1080\/07391102.2018.1556737","article-title":"Identification of potential inhibitors for Klebsiella pneumoniae carbapenemase-3: A molecular docking and dynamics study","volume":"37","author":"Malathi","year":"2019","journal-title":"J. Biomol. Struct. Dyn."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1593\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:26:53Z","timestamp":1760120813000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,7]]},"references-count":42,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["molecules28041593"],"URL":"https:\/\/doi.org\/10.3390\/molecules28041593","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,7]]}}}