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- W4309579482 abstract "Through structural optimization and ring fusion strategy, we designed a series of novel imidazo[1,2-a]pyrazine derivatives as potential tubulin inhibitors. These compounds displayed potent anti-proliferative activities (micromolar to nanomolar) against a panel of cancer cell lines (including HepG-2, HCT-116, A549 and MDA-MB-231 cells). Among them, compound TB-25 exhibited the strongest inhibitory effects against HCT-116 cells with an IC50 of 23 nM. Mechanism studies revealed that TB-25 could effectively inhibit tubulin polymerization in vitro, and destroy the dynamic equilibrium of microtubules in HCT-116 cells. In addition, TB-25 dose-dependently induced G2/M phase cell cycle arrest and apoptosis in HCT-116 cells. Furthermore, TB-25 suppressed HCT-116 cell migration in a concentration-dependent manner. Finally, molecular docking showed that TB-25 fitted well in the colchicine binding site of tubulin and overlapped nicely with CA-4. Collectively, these results suggest that TB-25 represents a promising tubulin inhibitor deserving further investigation." @default.
- W4309579482 created "2022-11-28" @default.
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- W4309579482 date "2022-12-01" @default.
- W4309579482 modified "2023-10-17" @default.
- W4309579482 title "Design, synthesis, and bioevaluation of imidazo [1,2–a] pyrazine derivatives as tubulin polymerization inhibitors with potent anticancer activities" @default.
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- W4309579482 doi "https://doi.org/10.1016/j.bmc.2022.117098" @default.
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