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??g/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??g/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? ?g/mL,and its activity was higher than that of the control drug oleanolic acid [IC₅₀=?3.16±0.21??g/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.