Antiproliferative and Pro-Apoptotic Activity and Tubulin Dynamics Modulation of 1 H -Benzimidazol-2-yl Hydrazones in Human Breast Cancer Cell Line MDA-MB-231.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, c1995-
    • Subject Terms:
      Antineoplastic Agents*/chemistry ; Antineoplastic Agents*/pharmacology ; Apoptosis*/drug effects ; Breast Neoplasms*/drug therapy ; Breast Neoplasms*/metabolism ; Breast Neoplasms*/pathology ; Hydrazones*/chemistry ; Hydrazones*/pharmacology ; Tubulin*/metabolism; Female ; Humans ; Benzimidazoles/pharmacology ; Benzimidazoles/chemistry ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Molecular Docking Simulation ; Molecular Structure ; Polymerization ; Structure-Activity Relationship ; Tubulin Modulators/pharmacology ; Tubulin Modulators/chemistry
    • Abstract:
      (1) Background: The aim of the work is the evaluation of in vitro antiproliferative and pro-apoptotic activity of four benzimidazole derivatives containing colchicine-like and catechol-like moieties with methyl group substitution in the benzimidazole ring against highly invasive breast cancer cell line MDA-MB-231 and their related impairment of tubulin dynamics. (2) Methods: The antiproliferative activity was assessed with the MTT assay. Alterations in tubulin polymerization were evaluated with an in vitro tubulin polymerization assay and a docking analysis. (3) Results: All derivatives showed time-dependent cytotoxicity with IC 50 varying from 40 to 60 μM after 48 h and between 13 and 20 μM after 72 h. Immunofluorescent and DAPI staining revealed the pro-apoptotic potential of benzimidazole derivatives and their effect on tubulin dynamics in living cells. Compound 5d prevented tubulin aggregation and blocked mitosis, highlighting the importance of the methyl group and the colchicine-like fragment. (4) Conclusions: The benzimidazole derivatives demonstrated moderate cytotoxicity towards MDA-MB-231 by retarding the initial phase of tubulin polymerization. The derivative 5d containing a colchicine-like moiety and methyl group substitution in the benzimidazole ring showed potential as an antiproliferative agent and microtubule destabilizer by facilitating faster microtubule aggregation and disrupting cellular and nuclear integrity.
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    • Grant Information:
      KP-06-H39/4. NATIONAL SCIENCE FUND OF BULGARIA
    • Contributed Indexing:
      Keywords: MDA-MB-231 cells; benzimidazol-2-yl hydrazones; cytotoxicity; mitotic blockage; tubulin polymerization
    • Accession Number:
      0 (Antineoplastic Agents)
      0 (Benzimidazoles)
      0 (Hydrazones)
      0 (Tubulin)
      0 (Tubulin Modulators)
    • Publication Date:
      Date Created: 20240525 Date Completed: 20240525 Latest Revision: 20240813
    • Publication Date:
      20240813
    • Accession Number:
      PMC11123699
    • Accession Number:
      10.3390/molecules29102400
    • Accession Number:
      38792260