Discovery of New CDDO-Imidazole Derivatives as Potential Antitumor Agents.

In the search for new CDDOs (2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid derivatives) with higher antitumor activity in vivo, thirty CDDO-imidazole derivatives (1-30) were designed and synthesized. Then, 8 was selected due to its superior anti-proliferative activity against three cancer cell lines (B16F10, A549, and HCT116) and its lower toxicity in zebrafish embryos compared to the other evaluated compounds. Further study found that 8 induced apoptosis in HCT116 cells by downregulating Bcl-2, upregulating Bax, and activating caspase-3 to kill cancer cells. Notably, 8 exhibited significant antitumor efficacy comparable to CDDO-Me (bardoxolone methyl), which had entered clinical trials. Taken together, 8 represents a promising candidate for the treatment of cancer and merits further study.