原子类型电拓扑指数在脂肪醇类化合物毒性预测研究中的应用  

Application of Electrotopological State Index for Atom Type to the Study of Aliphatic Alcohol Toxicity Prediction

作　　者：刘丽[1] 梅虎[1] 皮喜田[1] 龙瑞才[1] 李建[1] 李志良[1] 

机构地区：[1]重庆大学生物工程学院,重庆400030

出　　处：《化学学报》2008年第16期1873-1878,共6页Acta Chimica Sinica

基　　金：国家高技术研究发展计划"人易感致病性禽流感疫苗库设计及创新产品研发"(No.2006AA02Z312);教育部和国家外国专家局"高等学校学科创新引智计划"(No.[2005]7);重庆大学自然科学青年基金资助项目

摘　　要：采用原子类型电拓扑指数(ETSIAT)为结构描述子,对梨形四膜虫、番茄、红蜘蛛、发光细菌荧光素酶、呆鲦鱼以及鼠的脂肪醇毒性进行了定量构效关系(QSAR)研究.在偏最小二乘法建立QSAR模型的基础上,采用内部和外部两种验证方法对模型进行验证.研究结果表明:ETSIAT可以很好地表征脂肪醇与多种生物毒性相关的结构信息,所建模型具有良好的稳定性和外部预测能力.偏最小二乘模型分析结果显示:疏水性可能是影响脂肪醇毒性大小的主要因素,其毒性随C链长度的增加而增强,且相同C原子数的直链脂肪醇毒性明显高于支链脂肪醇;由于空间位阻效应,长链脂肪醇与短链脂肪醇可能存在不同的毒性作用机理。Electrotopological state index for atom type （ETSIAT） was employed in the quantitative structure-activity relationship （QSAR） studies on the aliphatic alcohol toxicity to the Tetrahymena pyriformis, tomato, spider, bacterial luciferases, Fathead minnow, and rat. The QSAR models were established by partial least squares and further validated by both internal and external validations. The results showed that ETSIAT can characterize the structural information relevant to aliphatic alcohol toxicity very well and the QSAR models established have good stabilities and prediction capabilities. From the PLS （partial least squares） analysis on the QSAR models, it can be seen that hydrophobicity is the decisive factor to affect the aliphatic alcohol toxicity. The aliphatic alcohol toxicity was enhanced with increasing the length of carbon chain, and the aliphatic alcohol toxicity of straight chain was higher than that of branched chain with the equal number of carbon atoms. Due to the steric effect, there may be different toxicity mechanisms between long-chain and short-chain aliphatic alcohols.

关 键 词：定量构效关系 原子类型电拓扑指数 脂肪醇 毒性 

分 类 号：O621.2[理学—有机化学]