Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases.
Miltirone analogues were synthesized and evaluated for inhibitory activity against Cdc25 and PTP1B. Most of the compounds demonstrated potent Cdc25 inhibitory activity, and several exhibited higher selectivity for Cdc25 than for PTP1B. In a cytotoxic assay, most of the compounds displayed cytotoxicity against the tumor cell lines A549 and HCT-116, producing IC(50) values in the micromolar range.
Huang
Weigang
W
The National Center for Drugs Screening, Shanghai Institute of Materia Medica, SIBS, Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Li
Jingya
J
Zhang
Wei
W
Zhou
Yueyang
Y
Xie
Chuanming
C
Luo
Yu
Y
Li
Yunfei
Y
Wang
Jingli
J
Li
Jia
J
Lu
Wei
W
D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D010616:Phenanthrenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D010616:Phenanthrenes; C068880:miltirone; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D020687:cdc25 Phosphatases