论文部分内容阅读
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。
Objective: To study the electronic structure of non-nucleoside reverse transcriptase inhibitors and its relationship with the inhibition of HIV activity. Methods: The dominant conformations and electronic structures of 24 nevirapine analogues were calculated by MM + method and semi-empirical MNDO method. The relationship between the electronic structure and the activity of HIV virus was also discussed. Results: The quantitative structure-activity relationship equation was obtained: pIC_ (50) = 6.101-53.669Q_4 + 15.980Q_7 + 0.259TA. The results also show that: these drugs inhibit HIV activity and the drug molecules 4 and 7 net charge Q_4 and Q7, the molecular structure of the 4 and 7 position is the active center of drug action, while the molecular The twist angle allows the active center of the molecule to be more suitable for binding to the molecule, resulting in HIV-inhibiting activity. Conclusion: The quantitative structure-activity relationship obtained can predict the activity of these compounds. The N atom at position 7 and the C atom at position 4 are the active centers of drug molecules.