Department of Occupational Safety and Health, College of Public Health, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan.
Department of Safety, Health and Environmental Engineering, National Kaohsiung University of Science and Technology, No.1, University Road, Yanchao District, Kaohsiung City 824, Taiwan.
Molecules. 2018 Apr 15;23(4):911. doi: 10.3390/molecules23040911.
The skin permeability () defines the rate of a chemical penetrating across the stratum corneum. This value is widely used to quantitatively describe the transport of molecules in the outermost layer of epidermal skin and indicate the significance of skin absorption. This study defined a quantitative structure-activity relationship (QSAR) based on 106 chemical substances of measured using human skin and interpreted the molecular interactions underlying transport behavior of small molecules in the stratum corneum. The QSAR developed in this study identified four molecular descriptors that described the molecular cyclicity in the molecule reflecting local geometrical environments, topological distances between pairs of oxygen and chlorine atoms, lipophilicity, and similarity to antineoplastics in molecular properties. This QSAR considered the octanol-water partition coefficient to be a direct influence on transdermal movement of molecules. Moreover, the QSAR identified a sub-domain of molecular properties initially defined to describe the antineoplastic resemblance of a compound as a significant factor in affecting transdermal permeation of solutes. This finding suggests that the influence of molecular size on the chemical's skin-permeating capability should be interpreted with other relevant physicochemical properties rather than being represented by molecular weight alone.
皮肤通透性（）定义了化学物质穿过角质层的速率。该值被广泛用于定量描述表皮最外层的分子迁移，并表明皮肤吸收的重要性。本研究基于 106 种用人皮测量的化学物质，定义了一个定量构效关系（QSAR），并解释了小分子在角质层中迁移行为的分子相互作用。本研究中开发的 QSAR 确定了四个分子描述符，这些描述符描述了反映局部几何环境的分子环状，氧和氯原子对之间的拓扑距离，亲脂性以及分子性质与抗肿瘤药的相似性。QSAR 将辛醇-水分配系数视为分子经皮迁移的直接影响因素。此外，QSAR 确定了最初定义为描述化合物抗肿瘤相似性的分子性质的子域，作为影响溶质经皮渗透的重要因素。这一发现表明，分子大小对化学物质皮肤渗透性的影响应该与其他相关物理化学性质一起解释，而不仅仅是用分子量来表示。
