Mehdipour Ahmad R, Hemmateenejad Bahram, Miri Ramin
Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, 71345-1149 Shiraz, Iran.
Chem Biol Drug Des. 2007 May;69(5):362-8. doi: 10.1111/j.1747-0285.2007.00506.x.
There has been an on-going debate about the mode of action of general anesthetics and until now, many sites have been postulated as target site for action of these compounds. Here, some quantum chemical-based quantitative structure-activity relationship (QSAR) models were developed for a set of polyhalogenated ethers in order to investigate the aspects of their anesthetic action, which is not completely defined yet, although some hypotheses have been suggested. A data set including 25 polyhalogenated methyl ethyl ethers were selected, and different descriptors were calculated for each molecule using density functional theory calculations, and subsequently some multilinear QSAR models were built by using different sets of the calculated molecular descriptors. The result showed that polar (polarizability) and non-polar (log P) parameters have mixed role on the anesthetic activity i.e. models with high statistical quality were obtained in combination with these two parameters. Also a good model between anesthetic action and electrostatic potentials was obtained, which may imply the important role of electronic interactions in the anesthetic activity of the compounds. Finally, a four-parametric QSAR model containing log P, molecular polarizability, most positive charge and an electrostatic potential parameters was obtained, which indicated that the anesthetic action of the polyhaloganted ethers may be proceeded through lipophilic, steric and columbic interactions.
关于全身麻醉药的作用方式一直存在争论，直到现在，许多位点都被假定为这些化合物的作用靶点。在此，为一组多卤代醚建立了一些基于量子化学的定量构效关系（QSAR）模型，以研究其麻醉作用的相关方面，尽管已经提出了一些假设，但麻醉作用尚未完全明确。选择了一个包含25种多卤代甲基乙基醚的数据集，使用密度泛函理论计算为每个分子计算不同的描述符，随后使用不同组计算得到的分子描述符建立了一些多线性QSAR模型。结果表明，极性（极化率）和非极性（log P）参数对麻醉活性具有混合作用，即结合这两个参数可得到具有高统计质量的模型。此外，还获得了麻醉作用与静电势之间的良好模型，这可能意味着电子相互作用在化合物的麻醉活性中起重要作用。最后，得到了一个包含log P、分子极化率、最大正电荷和静电势参数的四参数QSAR模型，这表明多卤代醚的麻醉作用可能通过亲脂性、空间位阻和库仑相互作用进行。
