title: Chalcones derivatives as potent Cell division cycle 25B phosphatase inhibitors.
abstract: 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 MTT 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.
authors.affiliation: Department of General Surgery, The Second Hospital, Jilin University, Changchun City, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Hospital, Jilin University, Changchun City, PR China.
authors.forename: Fu-Jian
authors.initials: FJ
authors.lastname: Ji
authors.affiliation: Department of General Surgery, The Second Hospital, Jilin University, Changchun City, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Gu
authors.affiliation: School of Public Health, Jilin University, Changchun City, PR China.
authors.forename: Xin-Yao
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Hospital, Jilin University, Changchun City, PR China. Electronic address: myzsmail@tom.com.
authors.forename: Shi-Xing
authors.initials: SX
authors.lastname: Qiao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D047188:Chalcones / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014407:Tumor Cells, Cultured; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D004791:Enzyme Inhibitors; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases
keywords: CDC25B; Chalcone derivatives; MTT methods; Phosphatase inhibitors