Computational repurposing of benzimidazole anthelmintic drugs as potential colchicine binding site inhibitors.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Author(s): Khattab M;Khattab M; Al-Karmalawy AA; Al-Karmalawy AA
  • Source:
    Future medicinal chemistry [Future Med Chem] 2021 Oct; Vol. 13 (19), pp. 1623-1638. Date of Electronic Publication: 2021 Sep 10.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Future Science Country of Publication: England NLM ID: 101511162 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1756-8927 (Electronic) Linking ISSN: 17568919 NLM ISO Abbreviation: Future Med Chem Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Future Science, 2009-
    • Subject Terms:
      Density Functional Theory*; Anthelmintics/*pharmacology ; Benzimidazoles/*pharmacology ; Colchicine/*antagonists & inhibitors; Anthelmintics/chemistry ; Benzimidazoles/chemistry ; Binding Sites/drug effects ; Colchicine/metabolism ; Drug Repositioning ; Molecular Docking Simulation ; Molecular Structure
    • Abstract:
      Background: Although some benzimidazole-based anthelmintic drugs are found to possess anticancer activity, their modes of binding interactions have not been reported. Methodology: In this study, we aimed to investigate the binding interactions and electronic configurations of nine benzimidazole-based anthelmintics against one of the well-known cancer targets (tubulin protein). Results: Binding affinities of docked benzimidazole drugs into colchicine-binding site were calculated where flubendazole > oxfendazole > nocodazole > mebendazole. Flubendazole was found to bind more efficiently with tubulin protein than other drugs. Quantum mechanics studies revealed that the electron density of HOMO of flubendazole and mebendazole together with their molecular electrostatic potential map are closely similar to that of nocodazole. Conclusion: Our study has ramifications for considering repurposing of flubendazole as a promising anticancer candidate.
    • Contributed Indexing:
      Keywords: CBSIs; DFT calculations; anthelmintics; drug repurposing; molecular docking; tubulin inhibitors
    • Accession Number:
      0 (Anthelmintics)
      0 (Benzimidazoles)
      SML2Y3J35T (Colchicine)
    • Publication Date:
      Date Created: 20210910 Date Completed: 20220131 Latest Revision: 20220131
    • Publication Date:
      20231215
    • Accession Number:
      10.4155/fmc-2020-0273
    • Accession Number:
      34505541