Department of Chemistry, Xavier University of Louisiana, New Orleans, USA.
SAR QSAR Environ Res. 2011 Oct;22(7-8):681-97. doi: 10.1080/1062936X.2011.623320. Epub 2011 Oct 17.
Quantitative structure-activity relationship (QSAR) studies were conducted on an in-house database of cytochrome P450 enzyme 1A2 inhibitors using the comparative molecular field analysis (CoMFA), comparative molecular similarity analysis (CoMSIA) and hologram QSAR (HQSAR) approaches. The database consisted of 36 active molecules featuring varied core structures. The model based on the naphthalene substructure alignment incorporating 19 molecules yielded the best model with a CoMFA cross validation value q(2) of 0.667 and a Pearson correlation coefficient r(2) of 0.976; a CoMSIA q(2) value of 0.616 and r(2) value of 0.985; and a HQSAR q(2) value of 0.652 and r(2) value of 0.917. A second model incorporating 34 molecules aligned using the benzene substructure yielded an acceptable CoMFA model with q(2) value of 0.5 and r(2) value of 0.991. Depending on the core structure of the molecule under consideration, new CYP1A2 inhibitors will be designed based on the results from these models.
采用比较分子场分析（CoMFA）、比较分子相似性分析（CoMSIA）和全息定量构效关系（HQSAR）方法，对细胞色素 P450 酶 1A2 抑制剂的内部数据库进行了定量构效关系（QSAR）研究。该数据库包含 36 种具有不同核心结构的活性分子。基于萘亚基排列的模型，包含 19 种分子，产生了最佳模型，CoMFA 交叉验证值 q(2)为 0.667，Pearson 相关系数 r(2)为 0.976；CoMSIA 的 q(2)值为 0.616，r(2)值为 0.985；HQSAR 的 q(2)值为 0.652，r(2)值为 0.917。第二个模型包含 34 种使用苯亚基排列的分子，产生了一个可接受的 CoMFA 模型，q(2)值为 0.5，r(2)值为 0.991。根据所考虑的分子的核心结构，将根据这些模型的结果设计新的 CYP1A2 抑制剂。
