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.