HEPT类HIV-1逆转录酶衍生物的CoMFA、CoMSIA及HQSAR研究

CoMFA, CoMSIA and HQSAR studies of HEPT as HIV-1 Reverse Transcriptase Inhibitors

摘要:

采用比较分子力场分析法（CoMFA）、比较分子相似因子分析法（CoMSIA）和分子全息定量结构关系（HQSAR）对1-[(2-羟乙氧)甲基]-6-苯硫基胸腺嘧啶(HEPT)类衍生物进行了分子活性构象选择、分子叠合、空间力场范围建立以及相应3D-QSAR模型建立。结果表明，该法所建模型对此类化合物具有良好的预测能力。CoMFA模型显示，交叉验证系数（q2）为0.565，非交互验证系数（r2）为0.892；CoMSIA模型显示，最佳q2为0.636， r2为0.953；最佳的HQSAR模型显示， q2为0.876， r2为0.929，最佳全息长度为97。根据三维等势图和HQSAR色码图设计了7个有较高活性的HEPT类化合物。

Abstract:

Comparative Molecular Field Analysis ( CoMFA), Comparative Molecular Similarity Indices Analysis (CoMSIA) and the hologram quantitative structure-activity relationship (HQSAR) for 1-[(2-hydroxyethyloxy)methyl]-6-phenylthio thymidine (HEPT) derivatives were used to have molecular active conformation selection，molecular alignment，as well as the establishment of corresponding 3D-QSAR model. The model established by this method has a good ability to predict these compounds. The cross-validated q2 value of CoMFA model is 0.565 and the non-cross-validated r2 value is 0.892. The best q2 value of CoMSIA Model is 0.636 and r2 value is 0.953. The most effective HQSAR model was obtained that the q2 value of 0.876, the r2 value of 0.929, and the best hologram length value is 97. Seven highly active HEPT compounds were designed based on the three-dimensional Contour maps and the HQSAR color code map, Observations derived from these QSAR modeling study may be provided a theoretical reference for designing more active HEPT derivatives.