5-((5-Nitrofuran-2-yl)allylidene)-2-thioxo-4-thiazolidinones Target Microtubules in Breast Cancer Cells

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Abstract
4-Thiazolidinone derivatives, a group of compounds with a broad spectrum of activity and anticancer properties, are used in medicine as anti-inflammatory, antiviral, antibacterial, antidiabetic, and blood pressure-lowering drugs; some of them are now in phase II and III clinical trials as anticancer drugs. Here, we evaluated the anticancer potential of 4-thiazolidinones (2b, 12b, 14b) targeting tubulin and metastasis-related pathways in breast cancer models. Molecular docking revealed that compound 14b exhibited the strongest binding affinity to the paclitaxel-binding site of β-tubulin, outperforming 2b and 12b, though slightly weaker than Taxol. Biological assays confirmed significant tubulin inhibition, with 14b reducing β-tubulin levels up to eight-fold in MCF-7 cells and two-fold in MDA-MB-231 cells. All compounds promoted tubulin polymerization, showing paclitaxel-like activity, with comparable the maximum velocity (Vmax) values. Cell cycle analysis demonstrated G2/M arrest in MCF-7 cells and S-phase accumulation in MDA-MB-231 cells. Overall, compound 14b demonstrated the most promising multitarget anticancer activity in vitro.
Funding Information
  • Uniwersytet Medyczny w Bialymstoku (B.SUB.24.242)
  • Uniwersytet Medyczny w Bialymstoku (B.SUB.23.158)
  • National Research Foundation of Ukraine (2023.05/0021)
  • National Research Foundation of Ukraine (2023.03/0104)

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