Synthesis and Biological Evaluation of 2´-Hydroxy-4´,6´-Diprenyloxychal-Cone Derivatives as Potent CDC25B and PTP1B Inhibitors

Abstract

A series of 2´-hydroxy-4´,6´-diisoprenyloxychalcone derivatives were synthesized and evaluated for inhibitory activities against CDC25B and PTP1B. The results displayed the most of them showed inhibitory activities against CDC25B (IC50=1.19–14.20 µg/mL) and PTP1B (IC50= 1.26–8.44µg /mL), respectively. Moreover, compound 2h displayed the most CDC25B and PTP1B inhibitory activity in vitro with IC50 values of 1.19 and 1.26 µg/mL, respectively, compared with reference drugs Na3VO4(IC50=1.09 µg/mL) and oleanolic acid (IC50=1.01 µg/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. Keywords: 2´-Hydroxy-4´, 6´-diprenyloxychalcone, synthesis, CDC25B, PTP1B, phosphatase inhibitors, enzyme kinetic.