In Silico Investigation of Phytochemicals From Clinically Tested Herbal Extracts as Potential Dihydrofolate Reductase Inhibitors for Buruli Ulcer.
Buruli ulcer (BU), a neglected tropical disease caused by Mycobacterium ulcerans, requires more effective and accessible treatments. Clinical trials have shown the efficacy of herbal formulations containing Nicotiana tabacum, Mangifera indica, Carica papaya, and Solanum rugosum, although the active...
| Publicado en: | BioMed Research International Vol. 2025; pp. 1 - 23 |
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| Autores principales: | , , , , , , , , , |
| Formato: | equations & formulas pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
9/3/2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=187725767&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 187725767 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 9/3/2025 vid: 2025 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 187725767 187725767 187725767 10.1155/bmri/4196295 187725767 ppf: 1 ppct: 22 formats: fmt: – @attributes: type: T – @attributes: type: C – @attributes: type: P tig: atl: In Silico Investigation of Phytochemicals From Clinically Tested Herbal Extracts as Potential Dihydrofolate Reductase Inhibitors for Buruli Ulcer. aug: au: Mohamed, Alkhair Adam Khalil Woasiedem, Tamekloe Appiah-Ofori, Philip Collins Adam, Esraa Mohammed Abdulmahmoud Obiri, Samuel Asiamah Borquaye, Lawrence Sheringham Adokoh, Christian K. Elamin, Ghazi Asiamah, Isaac Panja, Sourav affil: Department of Biomedical Sciences,, School of Allied Health Sciences,, College of Health and Allied Sciences,, University of Cape Coast,, Cape Coast, Ghana, ucc.edu.gh sug: subj: Plants, Medicinal Plant Extracts Phytochemicals Pharmacodynamics Folic Acid Antagonists Pharmacodynamics Buruli Ulcer Drug Therapy Molecular Docking Simulation Phytochemicals Analysis Trimethoprim Methotrexate Post Hoc Analysis Factor Analysis Phytochemicals Pharmacokinetics Deep Learning Molecular Structure Drug Toxicity Phytochemicals Administration and Dosage Phytochemicals Adverse Effects Hepatotoxicity Cardiotoxicity Mutagenicity Tests ab: Buruli ulcer (BU), a neglected tropical disease caused by Mycobacterium ulcerans, requires more effective and accessible treatments. Clinical trials have shown the efficacy of herbal formulations containing Nicotiana tabacum, Mangifera indica, Carica papaya, and Solanum rugosum, although the active phytochemicals remain unstudied. In the present study, we employed an in silico approach to identify the active phytochemicals from these plants that could inhibit M. ulcerans dihydrofolate reductase (MuDHFR), a crucial enzyme for mycobacterial survival. A library of 172 phytochemicals was screened using molecular docking, followed by 300‐ns molecular dynamics (MD) simulations using AMBER for the top hits and standard drugs (methotrexate and trimethoprim). Binding free energies were calculated using the molecular mechanics/generalized born surface area (MM/GBSA) method. The extended MD simulations and post hoc MM/GBSA analysis revealed that kaempferol‐3‐O‐rutinoside (ΔGbind −51.62 kcal/mol) and neochlorogenic acid (ΔGbind −49.44 kcal/mol) exhibited the strongest and most stable binding to MuDHFR. The binding energies were more favorable than both methotrexate (ΔGbind −44.18 kcal/mol) and trimethoprim (ΔGbind −41.01 kcal/mol) used as positive controls. Stability analyses (RMSD and RMSF) and principal component analysis (PCA) confirmed that these compounds form stable complexes and induce specific conformational states in the enzyme. Favorable ADMET profiles, particularly the lack of predicted skin sensitization, support their potential for topical use. This study identifies kaempferol‐3‐O‐rutinoside and neochlorogenic acid as the most promising lead candidates for developing novel BU therapies, warranting their prioritization for experimental validation. pubtype: Academic Journal doctype: equations & formulas pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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