| 引用本文: | 尤贤霞,周琴,胡雁,胡纯琦.喹啉酮类小分子p53-MDM2结合抑制剂3D-QSAR研究[J].中国现代应用药学,2013,30(9):963-969. |
| YOU Xianxia,ZHOU Qin,HU Yan,HU Chunqi.3D-QSAR Studies on Isoquinolinone Derivatives as Inhibitors of P53-MDM2 Binding[J].Chin J Mod Appl Pharm(中国现代应用药学),2013,30(9):963-969. |
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| 摘要: |
| 目的 设计、合成高活性的小分子p53-MDM2结合抑制剂，建立具有预测能力的3D-QSAR模型。方法 采用分子模拟软件Sybyl，利用比较分子场方法(CoMFA)、比较分子相似性指数法(CoMSIA)，选择已报道的具有p53-MDM2结合抑制活性的一类有相同母核的21个异喹啉酮衍生物作为训练集，7个作为预测集进行3D-QSAR模型的建立和验证。结果 模型具有较高q2(q2CoMFA=0.545，q2CoMSIA=0.528)和r2(r2CoMFA=0.984，r2CoMSIA=0.972)值，表明2组模型具有较高的拟和能力及预测能力。结论 该模型具有较高的预测能力，为设计、合成高活性的小分子p53-MDM2结合抑制剂提供了理论依据。 |
| 关键词: 比较分子场法 比较分子相似性指数法 p53-MDM2 结合抑制剂 异喹啉酮 |
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| 基金项目:浙江省自然科学基金青年项目(LQ13H300001) |
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| 3D-QSAR Studies on Isoquinolinone Derivatives as Inhibitors of P53-MDM2 Binding |
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YOU Xianxia1, ZHOU Qin1, HU Yan2, HU Chunqi3,2
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1.Chemistry&Chemical Engineering, Shaoxing University, Shaoxing 312000, China;2.Zhejiang University-Ecole Normale Superieure Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China;3.College of Chemistry&Chemical Engineering, Shaoxing University, Shaoxing 312000, China
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| Abstract: |
| OBJECTIVE To develop a predictable 3D-QSAR model for designing novel p53-MDM2 binding inhibitors. METHODS A series of isoquinolone derivatives inhibitors of p53-MDM2 binding were subjected to three-dimensional quantitative structureeactivity relationship (3D-QSAR) studies using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches. RESULTS The CoMFA model included steric and electrostatic fields for the training set with the cross validated q2 value of 0.545 and the non-cross-validated r2 value of 0.984. The cross-validated q2 value of CoMSIA model was 0.528 and the non-cross-vaildated r2 value was 0.972. CONCLUSION Based on the inoformation obtained from the model, this model is predictable and therefor more derivatives will be designed for further studies. |
| Key words: CoMFA CoMSIA p53-MDM2 binding inhibitor isoquinolone |
