Alert-QSAR. Implications for electrophilic theory of chemical carcinogenesis.
Alert-QSAR. Implications for electrophilic theory of chemical carcinogenesis.
复制标题
DOI：
10.3390/ijms12085098
复制
发表时间：
2011
影响因子：
5.6
通讯作者：
Ostafe V
中科院分区：
文献类型：
--
作者：
Putz MV;Ionaşcu C;Putz AM;Ostafe V
考虑到直接影响DNA的遗传毒性致癌物或诱变剂的定量结构活性关系(QSAR)的建模和预测能力，本研究调查了亲电分子结构与大鼠观察致癌活性(观察活性，A=Log[1/TD50])的结构警报(SA)中间预测相关性。本方法包括计算最近发展的结构告警模型的残差相关性，即。我们提出了一种特殊的亲电配体-受体机制，该机制结合了电负性与化学硬度相关的前沿原则、配体-试剂电负性的等同性和配体对特定受体的最大化学硬度。观察到的致癌活性受到SA诱变中间效应的影响，以及Hansch指数，如疏水性(LogP)、极化率(POL)和总能量(ETOT)，这些指数分别解释了分子膜扩散、离子变形和空间性。使用结构警示化学信息，并完全符合经济合作与发展组织的QSAR指导原则，讨论了突变作为遗传毒性致癌发展的第一步的可能的QSAR机制解释。
Given the modeling and predictive abilities of quantitative structure activity relationships (QSARs) for genotoxic carcinogens or mutagens that directly affect DNA, the present research investigates structural alert (SA) intermediate-predicted correlations ASA of electrophilic molecular structures with observed carcinogenic potencies in rats (observed activity, A = Log[1/TD50], i.e., ). The present method includes calculation of the recently developed residual correlation of the structural alert models, i.e., . We propose a specific electrophilic ligand-receptor mechanism that combines electronegativity with chemical hardness-associated frontier principles, equality of ligand-reagent electronegativities and ligand maximum chemical hardness for highly diverse toxic molecules against specific receptors in rats. The observed carcinogenic activity is influenced by the induced SA-mutagenic intermediate effect, alongside Hansch indices such as hydrophobicity (LogP), polarizability (POL) and total energy (Etot), which account for molecular membrane diffusion, ionic deformation, and stericity, respectively. A possible QSAR mechanistic interpretation of mutagenicity as the first step in genotoxic carcinogenesis development is discussed using the structural alert chemoinformation and in full accordance with the Organization for Economic Co-operation and Development QSAR guidance principles.
登录
查看更多内容
影响因子：
15
作者：
Ayers, PW;Parr, RG
通讯作者：
Parr, RG
影响因子：
--
作者：
Ferrari T;Gini G
通讯作者：
Gini G
影响因子：
5.6
作者：
Chicu, Sergiu A.;Putz, Mihai V.
通讯作者：
Putz, Mihai V.
影响因子：
3.1
作者：
Huijbregts, Mark A. J.;Rombouts, Linda J. A.;van de Meent, Dik
通讯作者：
van de Meent, Dik
影响因子：
--
作者：
Fjodorova N;Vracko M;Novic M;Roncaglioni A;Benfenati E
通讯作者：
Benfenati E