Chalcones derivatives as potent Cell division cycle 25B phosphatase inhibitors

To discover novel cell division cycle 25 (CDC25) B inhibitors and elucidate the mechanisms of inhibition in cancer cells. Nineteen 2'-hydroxy-4'-isoprenyloxychalcone derivatives (a-s) were evaluated the inhibition CDC25B activity. The enzymatic activities of the CDC25B catalytic domain were determined by monitoring the dephosphorylation of OMFP. Cell growth inhibition was detected by MIT assay. The results showed that sixteen compounds significantly inhibited cycle 25B phosphatase in vitro. Among, three compounds k, r and s had the best inhibition activity and significantly inhibited CDC25B with inhibition rates against CDC25B of 99.95%, 99.75%, and 97.77%, respectively, which is similar to the reference drugs Na3VO4 (98%). Cytotoxic activity assays showed compounds k and r are the potent against HCT116, HeLa, and A549 cells, moreover, compound k delayed the potent tumor inhibitory activity in a colo205 xenograft model in vivo. (c) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. Z o.o. All rights reserved.