Synthesis,Characterization And Evaluation Of Cdc25B/PTP1B Inhibitory Activity Of Novel Thiocarbohydrazone Derivatives Containing Carbazole/Carbazole-Isatin Moiety

1.In this paper,forty-nine novel target compounds,fourteen mono-/bis-thiocarbohydrazone derivatives containing carbazole moiety（TM-I-3a³n）and thiry-five thiocarbohydrazone derivatives containing carbazole-isatin moiety（TM-II-1³5）,were designed and synthesized.The structures of the target compounds were characterized by IR,¹H NMR,¹³C NMR、2D NMR and elemental analyses.2.The inhibitory activities of the target compounds TM-I-3a³n and TM-II-1³5 against Cdc25B/PTP1B were evaluated.The results are as follows:（1）In the target compounds TM-I-3a³n series,most of them exhibited inhibitory activities against Cdc25B with the inhibition rate of 79.87%⁹9.46%.Among them,compounds TM-I-3k was most potent with IC₅₀ value of（0.23±0.02）μg/mL against Cdc25B.Most of target compounds had strong inhibitory activity against PTP1B,and the inhibition rates were in the range of 53.09%⁹3.33%.Among them,the compound TM-I-3h exhibited the highest inhibitory activity,IC₅₀=（1.00±0.16）μg/mL.It is worth noting that compounds 3c,3f³h and 3j³n show high inhibitory activity against Cdc25B and PTP1B,and compound 3k had the highest activity.（2）In the target compound TM-II-1³5 series,all the target compounds showed good inhibitory activity against PTP1B with the inhibition rate of 89.34%⁹8.91%.Among them,the compound TM-II-6 had the highest inhibitory activity,IC₅₀=（0.65±0.05） μg/mL,and its activity was higher than that of the control drug oleanolic acid [IC₅₀=（3.16±0.21）μg/mL].3.The obtained research results in this paper will provide powerful basis for the development of novel Cdc25B and PTP1B inhibitors.The research of this thesis is of important significance.