New CDDO Arylboronate Ester Derivatives with High Selectivity and Low Toxicity

As an oleanolic acid derivative, CDDO-Me lacks selectivity for tumors. Based on the high Reactive Oxygen Species (ROS) level in Cancer cells, compound 4 was selected from 17 new CDDO arylboronate ester derivatives. A preliminary study revealed that 4 displayed the highest selectivity for Cancer cells. Furthermore, 4 could be transformed to 4H by ROS to increase its covalent binding ability and antiproliferation effect (IC₅₀ of 2.11 vs 0.37 μM) in BGC-823 cells. Interestingly, 4 increased ROS levels to induce Apoptosis in BGC-823 cells. Moreover, the LD₅₀ of 4 (91.2 mg/kg) was much greater than that of CDDO-Me (61.7 mg/kg) in ICR mice. A pharmacokinetic study indicated that 4 could be transformed to 4H in vivo. In addition, 4 exhibited a greater tumor inhibition rate (86.2%) than CDDO-Me (51.7%). Overall, the design of 4 provided an effective modification strategy for CDDO to increase the selectivity for Cancer cells.