Phosphorus-based SAHA analogues as histone deacetylase inhibitors

被引：52

作者：

Kapustin, GV

Fejér, G

Gronlund, JL

McCafferty, DG

Seto, E

Etzkorn, FA ^{[1
]}

机构：

[1] Virginia Tech, Dept Chem, Blacksburg, VA 24061 USA

[2] Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Mol Oncol Program, Tampa, FL 33612 USA

[3] Univ Penn, Sch Med, Johnson Res Fdn, Philadelphia, PA 19104 USA

[4] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA

来源：

ORGANIC LETTERS | 2003年 / 5卷 / 17期

关键词：

D O I：

10.1021/ol035056n

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

graphic Three analogues of suberoyl anilide hydroxamic acid (SAHA) with phosphorus metal-chelating functionalities were synthesized as inhibitors of histone deacetylases (HDACs). The compounds showed weak activity for HeLa nuclear extracts (IC50 = 0.57-6.1 mM), HDAC8 (IC50 = 0.28-0.41 mM), and histone-deacetylase-like protein (HDLP, IC50 = 0.33-1.9 mM), suggesting that the transition state of HDAC is not analogous to zinc proteases. Anti proliferative activity against A2780 cancer cells (IC50 = 0.11-0.12 mM), comparable to SAHA (0.15 mM), was observed.

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页码：3053 / 3056

页数：4

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