Chinese Journal of Organic Chemistry >
Synthesis and Bioactivity Study of Benzimidazole Derivatives with Fluorescent Self-Labeling and Tubulin Polymerization Inhibition
Received date: 2024-07-29
Revised date: 2024-09-14
Online published: 2024-10-29
Supported by
Key Scientific Research Program of the Higher Education Institutions of Henan Province(24A350001); Key Scientific and Technological Projects of Henan Province(242102310439)
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
Haiyang Dong , Jiaxin Pu , Keke Li , Haowen Zhang , Xiaoqing Geng , Tingting Liang , Jianhong Wang . Synthesis and Bioactivity Study of Benzimidazole Derivatives with Fluorescent Self-Labeling and Tubulin Polymerization Inhibition[J]. Chinese Journal of Organic Chemistry, 2025 , 45(4) : 1315 -1324 . DOI: 10.6023/cjoc202407044
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