Kuzu, BurakCakir, MustafaAcikgoz, EdaAlagoz, Mehmet Abdullah2025-09-032025-09-0320251860-71791860-718710.1002/cmdc.2025003202-s2.0-105012033926https://doi.org/10.1002/cmdc.202500320https://hdl.handle.net/20.500.14720/28350In the present study, the biological activities of novel compounds (BP-1 to BP-6), designed as antitubulin agents, were systematically evaluated, with a particular focus on their effects on the triple-negative breast cancer cell line MDA-MB-231 and non-cancerous cell line MCF-10A. BP-2 and BP-6 demonstrated micromolar-range antiproliferative activity against MDA-MB-231 cancer cells, with IC50 values of 8 and 4 mu M, respectively, comparable to nocodazole (3 mu M), and showed selective cytotoxicity over normal MCF-10A cells, with selectivity indices of approximately 3.3 and 8. In vitro analyses revealed that BP-2 and more notably BP-6 significantly inhibited cell proliferation in a time- and dose-dependent manner, disrupted microtubule organization through the downregulation of beta-tubulin expression, and induced apoptosis, as evidenced by increased levels of Cleaved Caspase-3 and distinct apoptotic morphological changes. Among the tested compounds, BP-6 exhibited the most potent antiproliferative and proapoptotic activity, with an IC50 value close to that of NOC. Molecular docking supported these findings by showing strong binding affinities of BP-6 to both beta-tubulin and Caspase-3, indicating a dual-targeted mechanism. Furthermore, molecular dynamics simulations confirmed the stable binding and dynamic integrity of BP-6 within both beta-Tubulin and Caspase-3 targets, underscoring its potential as a robust candidate for anticancer drug development.eninfo:eu-repo/semantics/openAccessAntitubulinApoptosisCancerCaspase-3Thiazolyl-PyrazoleArticleQ2Q240720621WOS:001538194200001