设计、合成及评估作为组蛋白去乙酰化酶抑制剂的贝林司他类似物。
Design, synthesis and evaluation of belinostat analogs as histone deacetylase inhibitors.
机构信息
School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, Jiangsu, China.
RCMI Cancer Research Center & Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA.
出版信息
Future Med Chem. 2019 Nov;11(21):2765-2778. doi: 10.4155/fmc-2018-0587. Epub 2019 Nov 8.
Abstract
Histone deacetylase (HDAC) is an attractive target for antitumor therapy. Therefore, the development of novel HDAC inhibitors is warranted. A series of HDAC inhibitors based on -hydroxycinnamamide fragment was designed as the clinically used belinostat analog using amide as the connecting unit. All target compounds were evaluated for their HDAC inhibitory activities and some selected compounds were tested for their antiproliferative activities. Among them, compound showed an IC value of 11.5 nM in inhibiting the HDAC in a pan-HDAC assay, being the most active compound of the series.
摘要
组蛋白去乙酰化酶（HDAC）是抗肿瘤治疗的一个有吸引力的靶点。因此，有必要开发新型的 HDAC 抑制剂。以 -羟基肉桂酰胺片段为基础，设计了一系列基于酰胺作为连接单元的 HDAC 抑制剂，作为临床使用的贝林司他类似物。所有的目标化合物都进行了 HDAC 抑制活性评价，一些选定的化合物进行了抗增殖活性测试。其中，化合物在泛 HDAC 测定中抑制 HDAC 的 IC 值为 11.5 nM，是该系列中最活跃的化合物。
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