1. Design, synthesis and biological evaluation of 1,2,3-triazole benzothiazole derivatives as tubulin polymerization inhibitors with potent anti-esophageal cancer activities.
- Author
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Wu, Bo-Wen, Huang, Wen-Jing, Liu, Yun-He, Liu, Qiu-Ge, Song, Jian, Hu, Tao, Chen, Ping, and Zhang, Sai-Yang
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BIOSYNTHESIS , *TRIAZOLE derivatives , *BENZOTHIAZOLE derivatives , *TUBULINS , *ONCOGENIC proteins , *BENZOXAZOLES - Abstract
In this work, we utilized the molecular hybridization strategy to design and synthesize novel 1,2,3-triazole benzothiazole derivatives K1-26. The antiproliferative activities against MGC-803, Kyse30 and HCT-116 cells were explored, and their structure-activity relationship were preliminarily conducted and summarized. Among them, compound K18 , exhibited the strongest proliferation inhibitory activity, with esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC 50 values were 0.042 and 0.038 μM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC 50 = 0.446 μM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based on these dual molecular-level effects, compound K18 could induce G2/M phase arrest and cell apoptosis in Kyse30 and EC-109 cells, as well as regulate the expression levels of cell cycle and apoptosis-related proteins. In summary, our findings highlight a novel 1,2,3-triazole benzothiazole derivative K18 , which possesses significant potential for treating esophageal cancers. [Display omitted] • Compound K18 showed low nanomolar IC 50 values of 0.042 and 0.038 μM against Kyse30 and EC-109 cells. • Compound K18 inhibited tubulin polymerization (EC 50 = 0.445 μM). • Compound K18 induced YAP degradation. • Compound K18 induced the G2/M phase arrest and apoptosis in Kyse30 and EC-109 cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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