Synthesis and Biological Evaluation of 2′-hydroxy-4′,6′-diprenyloxychal-Cone Derivatives as Potent CDC25B and PTP1B Inhibitors

A series of 2'-hydroxy-4',6'-diisoprenyloxychalcone derivatives were synthesized and evaluated for inhibitory activities against CDC25B and PTP1B. The results displayed that most of them showed inhibitory activities against CDC25B (IC50=1.19-14.20 mu g/mL) and PTP1B (IC50=1.26-8.44 mu g/mL), respectively. Moreover, compound 2h displayed the maximum CDC25B and PTP1B inhibitory activities in vitro with IC50 values of 1.19 and 1.26 mu g/mL, respectively, compared with reference drugs Na3VO4(IC50=0.9 mu g/mL) and oleanolic acid (IC50=1.0 mu g/mL). The results of selectivity experiments showed that the target compounds were selective inhibitors against CDC25B and PTP1B. Enzyme kinetic experiments demonstrated that compound 2h was a specific inhibitor with the typical characteristics of a mixed inhibitor.