QSAR studies on the anesthetic action of some polyhalogenated ethers.

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.