标题：Design and Synthesis of a Tetrahydroisoquinoline-Based Hydroxamate Derivative (ZYJ-34v), An Oral Active Histone Deacetylase Inhibitor with Potent Antitumor Activity
作者：Zhang, Yingjie; Liu, Chunxi; Chou, C. James; Wang, Xuejian; Jia, Yuping; Xu, Wenfang
作者机构：[Zhang, Yingjie; Xu, Wenfang] Shandong Univ, Dept Med Chem, Sch Pharm, Jinan 250012, Shandong, Peoples R China.; [Liu, Chunxi] Shandong Univ, Sch Ph 更多
通讯作者地址：[Xu, WF]Shandong Univ, Dept Med Chem, Sch Pharm, Jinan 250012, Shandong, Peoples R China.
来源：CHEMICAL BIOLOGY & DRUG DESIGN
关键词：antitumor; histone deacetylases; inhibitor; oral active;; tetrahydroisoquinoline; valproic acid
摘要：In our previous study, we developed a novel series of tetrahydroisoquinoline-based hydroxamic acid derivatives as histone deacetylase inhibitors (Bioorg Med Chem, 2010, 18, 1761-1772; J Med Chem, 2011, 54, 2823-2838), among which, compound ZYJ-34c (1) was identified and validated as the most potent one with marked in vitro and in vivo antitumor potency (J Med Chem, 2011, 54, 5532-5539.). Herein, further modification in 1 afforded another oral active analog ZYJ-34v (2) with simplified structure and lower molecular weight. Biological evaluation of compound 2 showed efficacious inhibition against histone deacetylase 1, 2, 3, and 6, which was confirmed by Western blot analysis results. Most importantly, compound 2 exhibited similar even more potent in vitro and in vivo antitumor activities relative to the approved histone deacetylase inhibitor SAHA.