Inhibitors of Human Histone Deacetylase: Synthesis and Enzyme and Cellular Activity of Straight Chain Hydroxamates
作者:Stacy W. Remiszewski、Lidia C. Sambucetti、Peter Atadja、Kenneth W. Bair、Wendy D. Cornell、Michael A. Green、Kobporn Lulu Howell、Manfred Jung、Paul Kwon、Nancy Trogani、Heather Walker
DOI:10.1021/jm015568c
日期:2002.2.1
Inhibitors of histone deacetylase (HDAC) have been shown to induce terminal differentiation of human tumor cell lines and to have antitumor effects in vivo. We have prepared analogues of suberoylanilide hydroxamic acid (SAHA) and trichostatin A and have evaluated them in a human HDAC enzyme inhibition assay, a p21(waf1) (p21) promoter assay, and in monolayer growth inhibition assays. One compound,
组蛋白脱乙酰基酶(HDAC)的抑制剂已显示出可诱导人肿瘤细胞系的终末分化,并在体内具有抗肿瘤作用。我们准备了辛二酰苯胺异羟肟酸(SAHA)和曲古抑菌素A的类似物,并已在人类HDAC酶抑制试验,p21(waf1)(p21)启动子试验和单层生长抑制试验中对其进行了评估。发现一种化合物4-(二甲基氨基)-N- [7-(羟基氨基)-7-氧庚基]-苯甲酰胺可不同地影响一组八个人类肿瘤细胞系的生长。