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Molecules. 2018 Apr 15;23(4). pii: E911. doi: 10.3390/molecules23040911.

Evaluating Molecular Properties Involved in Transport of Small Molecules in Stratum Corneum: A Quantitative Structure-Activity Relationship for Skin Permeability.

Author information

1
Department of Occupational Safety and Health, College of Public Health, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan. chencp@mail.cmu.edu.tw.
2
Department of Safety, Health and Environmental Engineering, National Kaohsiung University of Science and Technology, No.1, University Road, Yanchao District, Kaohsiung City 824, Taiwan. chch_chen@nkfust.edu.tw.
3
Department of Occupational Safety and Health, College of Public Health, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan. u100014014@cmu.edu.tw.
4
Department of Occupational Safety and Health, College of Public Health, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan. yen071013@gmail.com.

Abstract

The skin permeability (Kp) 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 Kp quantitative structure-activity relationship (QSAR) based on 106 chemical substances of Kp measured using human skin and interpreted the molecular interactions underlying transport behavior of small molecules in the stratum corneum. The Kp 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 Kp QSAR considered the octanol-water partition coefficient to be a direct influence on transdermal movement of molecules. Moreover, the Kp 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.

KEYWORDS:

antineoplastic property; application domain; molecular weight; octanol-water partition coefficient; quantitative structure-activity relationship; skin permeability

PMID:
29662033
PMCID:
PMC6017021
DOI:
10.3390/molecules23040911
[Indexed for MEDLINE]
Free PMC Article

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