Identification of novel human neutrophil elastase inhibitors from dietary phytochemicals using in silico and in vitro studies.

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  • Additional Information
    • Source:
      Publisher: Taylor & Francis Country of Publication: England NLM ID: 8404176 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-0254 (Electronic) Linking ISSN: 07391102 NLM ISO Abbreviation: J Biomol Struct Dyn Subsets: MEDLINE
    • Publication Information:
      Publication: June 2012- : Oxon, UK : Taylor & Francis
      Original Publication: Guilderland, NY : Adenine Press, [c1983-
    • Subject Terms:
    • Abstract:
      Human neutrophil elastase (HNE) has been well studied as a therapeutic target for inflammatory diseases for several decades. A variety of small-molecule HNE inhibitors have been well known, and their mode of binding at the active site of the enzyme has been determined, but none of them reached clinical trials except sivelestat. In this study, we intended to identify potent dietary phytochemicals that can target the active site of HNE by employing computational methods and in vitro inhibition assay. Database retrieval and preparation, structure-based virtual screening and molecular docking, rescoring, free energy calculations, adsorption, distribution, metabolism, and excretion (ADME) predictions and an in vitro assay were conducted to propose a collection of biochemically active molecules with the potential for inhibition against HNE. Overall, 167,504 secondary metabolites originating from the plants were docked. Of these, five natural compounds with drug-like properties have shown remarkable docking profiles to HNE. These hit candidates were then examined for validation through an HNE inhibition assay. The results showed that troxerutin (TX) had better binding efficacy with HNE followed by oleuropein, scutellarin, hesperidin and gossypin. These phytochemicals are present in relatively common fruits and vegetables, indicating the potential for safe and affordable inflammatory disease therapy.HighlightsTroxerutin shows the highest HNE binding affinity in computational analysis.HIS A: 57 is the major contributor to the protein-ligand interaction.Flavonoids exhibit binding efficacy against HNE.Flavonoids may serve as potent inhibitors for HNE.Communicated by Ramaswamy H. Sarma.
    • Contributed Indexing:
      Keywords: Human neutrophil elastase; phytochemicals; structure-based virtual screening
    • Accession Number:
      0 (Flavonoids)
      0 (Phytochemicals)
      0 (Proteinase Inhibitory Proteins, Secretory)
    • Publication Date:
      Date Created: 20201123 Date Completed: 20220422 Latest Revision: 20220520
    • Publication Date:
      20240105
    • Accession Number:
      10.1080/07391102.2020.1847685
    • Accession Number:
      33222615