Synthesis and biological testing of novel pyridoisothiazolones as histone acetyltransferase inhibitors
Synthesis and biological testing of novel pyridoisothiazolones as histone acetyltransferase inhibitors
复制标题
DOI：
10.1016/j.bmc.2011.01.063
复制
发表时间：
2011-06-15
影响因子：
3.5
通讯作者：
Sippl, Wolfgang
中科院分区：
文献类型：
--
作者：
Furdas, Silviya D.;Shekfeh, Suhaib;Sippl, Wolfgang
我们结合数据库筛选、合成和体外测试来鉴定新型组蛋白乙酰转移酶 (HAT) 抑制剂。美国国家癌症研究所化合物库 (NCI) 和几个商业数据库通过基于相似性的虚拟筛选进行筛选，以寻找新的 HAT 抑制剂。利用重组HAT p300/CBP相关因子(PCAF)和两种不同的组蛋白底物进行筛选，吡啶并异噻唑啉酮被鉴定为人PCAF的抑制剂。由于初始命中的溶解度有限，我们在 PCAF 上合成并测试了它们。这些化合物抑制癌细胞的增殖。总之，针对 HAT 作为新靶标的新型抗癌药物的有价值的化学工具和潜在的先导候选药物已经被确定。 (C) 2011 Elsevier Ltd. 保留所有权利。
We present a combination of database screening, synthesis and in vitro testing to identify novel histone acetyltransferase (HAT) inhibitors. The National Cancer Institute compound collection (NCI) and several commercial databases were filtered by similarity-based virtual screening to find new HAT inhibitors. Employing the recombinant HAT p300/CBP-associated factor (PCAF) and two different histone substrates for screening, pyridoisothiazolones were identified as inhibitors of human PCAF. Due to the limited solubility of the initial hits, we synthesized and tested them on PCAF. The compounds inhibit the proliferation of cancer cells. In summary, valuable chemical tools and potential lead candidates for new anticancer agents directed against HATs as new targets have been identified. (C) 2011 Elsevier Ltd. All rights reserved.