一类细胞凋亡诱导剂的结构特征研究

被引：1

作者：

张静晓 ^{[1
]}

李燕 ^{[1
]}

付新梅 ^{[2
]}

潘艳秋 ^{[1
]}

杨凌 ^{[3
]}

机构：

[1] 大连理工大学化工学院

[2] 大连理工大学精细化工国家重点实验室

[3] 中国科学院大连化学物理研究所药物资源开发研究组

来源：

大连理工大学学报 | 2015年 / 55卷 / 01期

关键词：

细胞凋亡诱导剂; caspase激活作用; 三维定量构效关系(3D-QSAR); 比较分子力场法(CoMFA); 比较分子相似性指数法(CoMSIA);

D O I：

暂无

中图分类号：

R73-36 [治疗实验]; Q255 [细胞的衰老与死亡];

学科分类号：

100214 ; 071009 ; 090102 ;

摘要：

许多抗癌药物通过引起癌细胞的凋亡来达到治疗目的,因此开发能诱导癌细胞凋亡的药物一直是癌症研究的热点.以153个结构各异的具有caspase-3激活作用的细胞凋亡诱导剂为研究对象,通过三维定量构效关系(3D-QSAR)分析,得到了一个基于位阻场、静电场、疏水场、氢键供体场和受体场参数的最优比较分子相似性指数法(CoMSIA)模型.该模型(Q2=0.51、R2ncv=0.89和R2pred=0.82)具有良好的内部一致性和预测能力,通过对模型的等值线图分析发现:(1)R2取代基提高诱导剂活性的因素包括位阻大、负电性大、有亲水性和具有氢键供体作用;(2)位阻适中和/或具有氢键供体作用的R4取代基,以及位阻小和/或亲水的R1取代基对提高分子的活性是有利的;(3)N-甲基-N-苯基-1-萘胺类细胞凋亡诱导剂具有正电性的A环3号位或C环7号位取代基,以及具有负电性的B环1号位取代基有利于提高诱导剂的生物活性.对该模型的分析更有利于认识细胞凋亡诱导剂的分子特征,并为设计和开发新型细胞凋亡诱导剂提供理论指导.

引用

页码：7 / 14

页数：8

共 14 条

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