基于间苯二甲酸的 HDAC 抑制剂作为曼氏血吸虫 HDAC8 的有效抑制剂。
Isophthalic Acid-Based HDAC Inhibitors as Potent Inhibitors of HDAC8 from Schistosoma mansoni.
机构信息
Institute of Pharmaceutical and Medicinal Chemistry, Heinrich-Heine-University, Düsseldorf, Germany.
Institute of Pharmaceutical Sciences, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
出版信息
Arch Pharm (Weinheim). 2017 Aug;350(8). doi: 10.1002/ardp.201700096. Epub 2017 Jun 22.
Schistosoma mansoni histone deacetylase 8 (SmHDAC8) has been recently identified as a new potential target for the treatment of schistosomiasis. A series of newly designed and synthesized alkoxyamide-based and hydrazide-based HDAC inhibitors were tested for inhibitory activity against SmHDAC8 and human HDACs 1, 6, and 8. The front runner compounds showed submicromolar activity against SmHDAC8 and modest preference for SmHDAC8 over its human orthologue hHDAC8. Docking studies provided insights into the putative binding mode in SmHDAC8 and allowed rationalization of the observed selectivity profile.
曼氏血吸虫组蛋白去乙酰化酶 8（SmHDAC8）最近被鉴定为治疗血吸虫病的一个新的潜在靶点。一系列新设计和合成的烷氧基酰胺基和酰肼基 HDAC 抑制剂被测试了对 SmHDAC8 和人源 HDACs 1、6 和 8 的抑制活性。前导化合物对 SmHDAC8 表现出亚微摩尔的活性，对 SmHDAC8 比对其人类同源物 hHDAC8 有适度的偏好。对接研究提供了 SmHDAC8 中假定的结合模式的见解，并允许对观察到的选择性概况进行合理化。
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