Synthesis and Bioactivity Evaluation of Benzimidazole Derivatives with Fluorescent Self-labeling and Tubulin Polymerization Inhibition

doi:10.6023/cjoc202407044

Chinese Journal of Organic Chemistry Previous Articles Next Articles

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兼具荧光自标记和微管蛋白聚合抑制作用的苯并咪唑衍生物合成及生物活性研究

冬海洋, 蒲佳欣, 李珂珂, 张昊文, 耿晓晴, 梁停停^*, 王建红^*

河南大学天然药物创新与转化重点实验室开封 475004

收稿日期:2024-07-29 修回日期:2024-09-14
基金资助:
基金目:河南省高等学校重点研究项目(No. 24A350001); 河南省科技攻关项目(No. 242102310439).

Synthesis and Bioactivity Evaluation of Benzimidazole Derivatives with Fluorescent Self-labeling and Tubulin Polymerization Inhibition

Dong Haiyang, Pu Jiaxin, Li Keke, Zhang Haowen, Geng Xiaoqing, Liang Tingting^*, Wang Jianhong^*

Henan Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng 475004

Received:2024-07-29 Revised:2024-09-14
Contact: * E-mail: liangting910710@126.com (T. Liang), hdky@henu.edu.cn (J. Wang)

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Abstract

A series of novel Combretastatin A-4-based benzimidazole derivatives were designed and synthesized according to rational drug design strategies. The antiproliferation activities were preliminarily evaluated against cancer cell line HT-29, and compound IV-02 stood out from the target compounds and exhibited significant antiproliferation potency. Further evaluation on multiple cancer cell lines such as HT-1080, HepG2, A549 and A549/Taxol cells, demonstrated that compound IV-02 showed significant cell growth inhibition on A549 cells with IC₅₀ of 0.18 µmol/L, which was comparable to that of positive control Colchicine (IC₅₀= 0.15 µmol/L). Further mechanistic studies demonstrated that IV-02 could inhibit tubulin polymerization in a concentration-dependent manner, cause cell cycle arrest in G2/M phase and induce the cell apoptosis. In addition, IV-02 exhibited fluorescence emission effect, which would be beneficial to label the intracellular dynamic changes of IV-02 in real time. The results indicated that compound IV-02 could serve as an anticancer compound with fluorescent self-labeling properties.

Key words: benzimidazole, tubulin, antitumor effect, fluorescence emission

Cite this article

Dong Haiyang, Pu Jiaxin, Li Keke, Zhang Haowen, Geng Xiaoqing, Liang Tingting, Wang Jianhong. Synthesis and Bioactivity Evaluation of Benzimidazole Derivatives with Fluorescent Self-labeling and Tubulin Polymerization Inhibition[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202407044.

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兼具荧光自标记和微管蛋白聚合抑制作用的苯并咪唑衍生物合成及生物活性研究

Synthesis and Bioactivity Evaluation of Benzimidazole Derivatives with Fluorescent Self-labeling and Tubulin Polymerization Inhibition

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