Font M, Monge A, Ruiz I, Heras B
Dpt. of Medicinal Chemistry, Centro de Investigación en Farmacobiologia Aplicada, Universidad de Navarra, Pamplona, España.
Drug Des Discov. 1997 Apr;14(4):259-72.
The relationship between the chemical structure and the HIV-1 RT inhibitory activity has been studied for a series of quinoline derivatives. Two methods were used: a standard QSAR analysis, by combining the methods of Hansch and Free-Wilson, and an analysis using quantum chemistry indices as descriptor parameters, by the semiempirical method AM1. The equations obtained lead to the proposal that the activity of the compounds increases, mainly, with the presence of electron-withdrawing substituents in position 6 of the quinoline ring that cause a decrease in the energy from the molecular orbital LUMO. In turn, this fact leads to the proposal that the most important interaction of these compounds with the HIV-1 RT is a charge transfer type interaction, with the quinoline aromatic ring acting as acceptor.
针对一系列喹啉衍生物，研究了其化学结构与HIV-1逆转录酶（RT）抑制活性之间的关系。采用了两种方法：一种是标准的定量构效关系（QSAR）分析，即将Hansch方法和Free-Wilson方法相结合；另一种是通过半经验方法AM1，使用量子化学指标作为描述参数进行分析。所得方程表明，化合物的活性主要随着喹啉环6位上吸电子取代基的存在而增加，这些取代基会导致分子轨道最低未占轨道（LUMO）能量降低。相应地，这一事实表明这些化合物与HIV-1 RT最重要的相互作用是电荷转移型相互作用，喹啉芳香环作为受体。
