非核苷类逆转录酶抑制剂抗HIV活性与其分子结构的关系

Study on the structure-activity relationships of nevirapine molecules of HIV inhibitors

目的:研究非核苷类逆转录酶抑制剂的电子结构与其抑制HIV病毒活性的关系。方法:应用分子力学MM+方法,半经验量子化学MNDO法计算了24个奈韦拉平(nevirapine)类似物的优势构象和电子结构,讨论这类药物的电子结构与其抑制HIV病毒活性的关系。结果:得到其抑制HIV活性与电子结构的定量构效关系方程:pIC_(50)=6.101-53.669Q_4+15.980Q_7+0.259TA。结果还表明:这类药物抑制HIV病毒活性与药物分子4号位和7号位上的净电荷Q_4和Q_7有关,分子结构上的4号与7号位是药物作用的活性中心,而分子的扭转角则让分子活性中心处于更适合于与分子结合的位置上,从而产生抑制HIV的活性。结论:所得到的定量构效关系能预测该类化合物的活性,分子中的7号位N和4号位C原子是药物分子的活性中心。

To analyze the QSAR of 24 nevirapine HIV Inhibitors, the MM + geometry optimization and MNDO quantum chemical indexes had been performed. The significant QSAR equation can be obtained as below:pIC_(50) =6.101 - 53.669Q_4 + 15.980Q_7 + 0.259TA The results show that the activities of nevirapine derivators are related with Q4 and Q7 of compound molecules.Objective: To study the structure-activity relationship of nevirapine derivatives. Methods: By using the MM + geometry optimization and MNDO quantum chemical methods, the QSAR and active sites of nevirapine derivatives were discussed. Results: It is found that their net charges Q_4 at position 4 and Q_7 at position 7 were concerned with the activity. The quantitative structure-activity relationship was established as LIC_(50) =6.101 - 53.669Q_4 + 15.980Q_7 + 0.259TA. While the molecular rotating angle TA was a certain value so that atoms at position 4 and 7 could combine with acceptor, the activity was raised. Conclusions:The inhibition activity of the nevirapine derivatives can be predicated by QSAR. The nitrogen 7 and carbon 4 are important active sites of the nevirapine derivatives.