The cell division cycle 25 phosphatase B (Cdc25B) is involved in carcinogenic transformation and is a potential drug target for anticancer therapy. In order to screen Cdc25B inhibitors, 1,3-selenazole was selected as the core block, and 1,2,4-triazole Schiff base was bridged into 2-(1,2,4-triazol-3-yl)thio-N-(4-phenyl-1,3-selenazolyl-2-yl)acetamide (TATS) by the amide thioether bond. The molecular docking simulation of TATS1 with Cdc25B was first performed to identify the rationality of the core function of 1,3-selenazole. The results show that 1,3-selenazole can be tightly embedded in the Cdc25B structure and perform N-H…PI non-bond weak interaction with the important catalytic site Arg492, which indicates that 1,3-selenazole plays a central role. The amide carbonyl oxygen atom forms a hydrogen bond with Arg492 and Arg488, indicating that the introduction of the amide thioether bond is reasonable. Based on the theoretical docking study, thirteen new target compounds TATS1~TATS13 were designed and synthesized through modification in two regions of 1,2,4-triazole Schiff base. The inhibition against Cdc25B of target molecules and important intermediates was tested respectively. As a result, the inhibitory activities of the intermediates are not good, 12 target compounds have better biological activity than the positive reference substance Na₃VO₄, the modifications of two regions of 1,2,4-triazole also have a significant effect, which suggests that these compounds are expected to be a potential inhibitor of Cdc25B.

Key words: 1,3-selenazole, 1,2,4-triazole Schiff base, molecular docking simulation, Cdc25B inhibitor