CuI-mediated synthesis of 1-aryl-5,6,7-trimethoxybenzimidazoles as potent antitubulin agents.
Cong-Min PengShih-Wei Wang LYi-Lin HwangWen-Chun SunLi-Pin ChiuYi-Ting LiuYu-Wei LaiHsueh-Yun LeePublished in: RSC advances (2023)
In situ CuI-mediated cyclization methodology helped yield benzimidazoles with different substitution manner, such as 1,2-diarylbenzimidazoles (4 and 5) and 1-arylbenzimidazoles (6-15). The result of structure-activity relationship (SAR) study confirmed the significance of the 5,6,7-trimethoxybenzimidazole moiety, and the representative derivatives (8-10) exhibited marked antiproliferative activity against A549, HCT-116, and PC-3 cells; in addition, they are able to inhibit the polymerization of tubulin. Among them, compound 10 inhibited the growth of A549, HCT-116, and PC-3 cells with a mean IC 50 value of 0.07 μM, and its IC 50 value of tubulin polymerization is 0.26 μM.