Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases

Weigang Huang; Jingya Li; Wei Zhang; Yueyang Zhou; Chuanming Xie; Yu Luo; Yunfei Li; Jingli Wang; Jia Li; Wei Lu

doi:10.1016/j.bmcl.2005.12.080

Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases

Bioorg Med Chem Lett. 2006 Apr 1;16(7):1905-8. doi: 10.1016/j.bmcl.2005.12.080. Epub 2006 Jan 24.

Authors

Weigang Huang¹, Jingya Li, Wei Zhang, Yueyang Zhou, Chuanming Xie, Yu Luo, Yunfei Li, Jingli Wang, Jia Li, Wei Lu

Affiliation

¹ 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.

PMID: 16434190
DOI: 10.1016/j.bmcl.2005.12.080

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Drug Screening Assays, Antitumor
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Phenanthrenes / chemical synthesis*
Phenanthrenes / chemistry
Phenanthrenes / pharmacology*
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Protein Tyrosine Phosphatases / antagonists & inhibitors
cdc25 Phosphatases / antagonists & inhibitors*

Substances

Enzyme Inhibitors
Phenanthrenes
miltirone
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Protein Tyrosine Phosphatases
cdc25 Phosphatases