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个人信息Personal Information
教授
硕士生导师
性别：女
毕业院校：九州工业大学
学位：博士
所在单位：生物工程学院
学科：生物工程与技术. 生物化学与分子生物学. 药剂学
办公地点：生物工程学院（西部校区）
A novel series of L-2-benzyloxycarbonylamino-8-(2-pyridyl)-disulfidyloctanoic acid derivatives as histone deacetylase inhibitors: Design, synthesis and molecular modeling study
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论文类型：期刊论文
发表时间：2012-06-01
发表刊物：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
收录刊物：SCIE、PubMed、Scopus
卷号：52
页面范围：111-122
ISSN号：0223-5234
关键字：Histone deacetylase; Histone deacetylase inhibitor; Docking; Molecular dynamics
摘要：Histone deacetylases inhibitors (HDACIs) have become an attractive class of anticancer agents. In order to find some novel potent HDACIs, we designed and synthesized a series of L-2-benzyloxycarbonylamino-8-(2-pyridyl)-disulfidyloctanoic acid derivatives. All compounds exhibited potent HDAC-inhibitory activity, and two of them had similar potency to TSA. The introduction of 2-amino-4-phenylthiazole or 9-methyleneoxy-fluorenyl group at the surface recognize domain of these HDACIs could greatly increase their HDAC-inhibitory activity. Molecular modeling studies indicated that coordination of the zinc ion by these inhibitors, and formation of hydrogen bond and hydrophobic interaction between inhibitors and HDACs were essential for the HDAC-inhibitory activities of these inhibitors. Asp181, Asp269, Leu276 and Tyr308 in the active site of HDAC2 gave favorable contributions for binding with all compounds. (C) 2012 Elsevier Masson SAS. All rights reserved.