In silico evaluations of phytochemicals from Withania somnifera exhibiting anticancer activity against NAD[P]H-quinone oxidoreductase.
Background: Cancer is a leading cause of death globally and in the US, prompting research into medicinal plants with anticancer properties. Withania somnifera, or Ashwagandha, is one such plants, known for its diverse pharmacological effects. Withaferin A and Viscosalactone B are two compounds found...
| Publicado en: | Human & Experimental Toxicology Vol. 43; pp. 1 - 21 |
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| Autores principales: | , , , , , , |
| Formato: | equations & formulas pictorial research tables/charts Journal Article |
| Publicado: |
Sage Publications Inc.
Nov2024
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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=190862403&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 190862403 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09603271 DZA jtl: Human & Experimental Toxicology issn: 09603271 maglogo: Y pubinfo: dt: Nov2024 vid: 43 pid: 344 pub: Sage Publications Inc. place: Thousand Oaks, California artinfo: ui: 190862403 190862403 190862403 10.1177/09603271241291399 190862403 ppf: 1 ppct: 20 formats: tig: atl: In silico evaluations of phytochemicals from Withania somnifera exhibiting anticancer activity against NAD[P]H-quinone oxidoreductase. aug: au: Jahagirdar, Sushma Praveen Kumar, Harshini Bhat, Smitha S Poddar, Arpita Chattaraj, Pratim Kumar Ahmad, Sheikh F Prasad, Shashanka K affil: Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru, India sug: subj: Phytochemicals Plant Extracts Therapeutic Use Antineoplastic Agents Enzyme Inhibitors Pharmacodynamics Oxidoreductases Drug Effects Plants, Medicinal Therapeutic Use Computer Simulation Human In Vitro Studies Molecular Docking Simulation Descriptive Statistics Molecular Structure Cell Line, Tumor Drug Effects Blood-Brain Barrier Drug Effects Cell Proliferation Bioinformatics Data Analysis Software Funding Source ab: Background: Cancer is a leading cause of death globally and in the US, prompting research into medicinal plants with anticancer properties. Withania somnifera, or Ashwagandha, is one such plants, known for its diverse pharmacological effects. Withaferin A and Viscosalactone B are two compounds found in Ashwagandha with known anticancer activity. The protein NQO1, overexpressed in various cancers, was the focus of this study. Hypothesis and aim: We hypothesize that specific phytochemicals in Withania somnifera can effectively interact with and inhibit the NQO1 protein, thereby exhibiting anticancer properties. This study aims to identify these interactions using in silico approaches. Methodology: CFDT was performed using the Gaussian 16 program package, followed by QSAR analysis of the compounds in the PASS online web server. The Schrodinger suite was used to carry out ligand and protein preparation, molecular docking, and molecular dynamic simulation to analyse the interaction of these compounds with NQO1 and ADME studies. Protox-II and SWISSADME tools were used to predict the toxicity and blood–brain barrier permeability of the phytochemicals. Results and conclusion: CDFT and frontier molecular orbital analyses predicted the stability and reactivity of all the selected molecules. QSAR analysis predicted the biological activity and toxicity of the compounds. Withaferin A exhibited the highest glide gscore (−4.953 kcal/mol) and demonstrated 6 hydrogen bond interactions with NQO1, suggesting its potential as an anticancer agent. Conceptual density functional theory-based analysis suggested the strong electrophilicity of the ligands, further supporting their potential anticancer activities. Viscosalactone B, another phytochemical from Ashwagandha, also showed interactions involving 6 hydrogen bonds with NQO1, with a glide gscore of (−4.593 kcal/mol). Molecular dynamic simulations validated the stability of the Withaferin A-NQO1 complex. ADME-T properties predicted high oral absorption for the selected ligands, indicating that Withaferin A could be a viable orally administered drug. 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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