| 氧肟酸类组蛋白去乙酰化酶抑制剂的药效团模型研究 |
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| 作者姓名： | YU Liqin LIU Fei CHEN Yadong YOU Qidong |
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| 作者单位： | Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Medicinal Chemistry, ;China Pharmaceutical University, Nanjing, Jiangsu 210009, China ; |
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| 摘 要： | 基于24个目前已知的氧肟酸类组蛋白去乙酰化酶抑制剂,我们运用Catalyst软件建立了一个三维药效团模型。其中,最好的药效团模型1,包含了四个化学特征（一个氢键供体,一个芳环和两个疏水基）,相关系数达到0.946,并由另外20个化合物进行了测试验证。我们第一次特征性描述了组蛋白去乙酰化酶的帽子（CAP）部分。我们的研究结果对于设计全新组蛋白去乙酰化酶抑制剂具有很好的指导作用。
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| 关 键 词： | anticancer hydroxamate histone deacetylase inhibitor hydroxamate pharmacophore modeling |
| 收稿时间： | 2008-5-29 |
| 修稿时间： | 2008-8-21 |
Pharmacophore Identification of Hydroxamate HDAC 1 Inhibitors |
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| YU Liqin,LIU Fei,CHEN Yadong,YOU Qidong.Pharmacophore Identification of Hydroxamate HDAC 1 Inhibitors[J].Chinese Journal of Chemistry,2009,27(3):557-564. |
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| Authors: | Liqin YU Fei LIU Yadong CHEN Qidong YOU |
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| Institution: | 1. Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009, China;2. Tel.: 0086‐025‐83271351;3. Fax: 0086‐025‐83271351 |
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| Abstract: | A three‐dimensional pharmacophore model was established based on 24 hydroxamate histone deacetylase (HDAC) inhibitors by HypoGen algorithm embedded in Catalyst software. The best pharmacophore hypothesis (Hypo1), consisting of four chemical features (one hydrogen‐bond acceptor, one aromatic ring and two hydrophobic groups), has a correlation coefficient of 0.946. The Hypol was also validated by a test set consisting of 20 other compounds. Compared with the prior studies towards HDAC inhibitors the detailed chemical features of the "CAP" region in the reported HDAC inhibitors were for the first time depicted, which would be helpful in the further designing of novel HDAC inhibitors. |
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| Keywords: | anticancer hydroxamate histone deacetylase inhibitor hydroxamate pharmacophore modeling |
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