CuI-mediated synthesis of 1-aryl-5,6,7-trimethoxybenzimidazoles as potent antitubulin agents

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.