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首页> 外文期刊>Bioorganic and medicinal chemistry >Three-dimensional quantitative structure-activity relationship studies on novel series of benzotriazine based compounds acting as Src inhibitors using CoMFA and CoMSIA.
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Three-dimensional quantitative structure-activity relationship studies on novel series of benzotriazine based compounds acting as Src inhibitors using CoMFA and CoMSIA.

机译：使用CoMFA和CoMSIA对新型系列苯并三嗪类化合物作为Src抑制剂的三维定量构效关系研究。

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Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of benzotriazine derivatives, as Src inhibitors. Ligand molecular superimposition on the template structure was performed by database alignment method. The statistically significant model was established of 72 molecules, which were validated by a test set of six compounds. The CoMFA model yielded a q(2)=0.526, non cross-validated R(2) of 0.781, F value of 88.132, bootstrapped R(2) of 0.831, standard error of prediction=0.587, and standard error of estimate=0.351 while the CoMSIA model yielded the best predictive model with a q(2)=0.647, non cross-validated R(2) of 0.895, F value of 115.906, bootstrapped R(2) of 0.953, standard error of prediction=0.519, and standard error of estimate=0.178. The contour maps obtained from 3D-QSAR studies were appraised for activity trends for the molecules analyzed. Results indicate that small steric volumes in the hydrophobic region, electron-withdrawing groups next to the aryl linker region, and atoms close to the solvent accessible region increase the Src inhibitory activity of the compounds. In fact, adding substituents at positions 5, 6, and 8 of the benzotriazine nucleus were generated new compounds having a higher predicted activity. The data generated from the present study will further help to design novel, potent, and selective Src inhibitors as anticancer therapeutic agents.
机译：对作为Src抑制剂的一系列苯并三嗪衍生物进行了比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）。通过数据库比对方法在模板结构上进行配体分子叠加。建立了由72个分子组成的具有统计学意义的模型，该模型已通过六种化合物的测试集进行了验证。 CoMFA模型产生的aq（2）= 0.526，未经交叉验证的R（2）为0.781，F值为88.132，自举R（2）为0.831，预测的标准误差为= 0.587，估计的标准误差为0.351，而CoMSIA模型产生了最佳的预测模型，其中aq（2）= 0.647，非交叉验证的R（2）为0.895，F值为115.906，自举R（2）为0.953，预测的标准误为0.519和标准误的估计值= 0.178。评估了从3D-QSAR研究获得的轮廓图，以分析分子的活性趋势。结果表明，疏水区域中较小的空间体积，芳基连接体区域附近的吸电子基团以及靠近溶剂可及区域的原子均增加了化合物的Src抑制活性。实际上，在苯并三嗪核的5、6和8位上添加取代基产生了具有更高预测活性的新化合物。本研究产生的数据将进一步帮助设计新颖，有效和选择性的Src抑制剂作为抗癌治疗剂。

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