شماره ركورد كنفرانس :
3976
عنوان مقاله :
Three-dimensional quantitative structure activity relationship modeling of the rate of penetration of diverse compounds through the human skin by using GRIND descriptors
پديدآورندگان :
Rezaei Soheila soheila.rezaei@ut.ac.ir University of Tehran , Ghasemi Jahan. B University of Tehran , Behnejad Hassan University of Tehran
كليدواژه :
skin permeability , 3D , QSAR , GRIND , molecular weight , logkp
عنوان كنفرانس :
ششمين سمينار ملي دوسالانه كمومتريكس ايران
چكيده فارسي :
The control of permeation is vital for the topical application of lotions, creams, and
ointments, and for the toxicological and danger assessment of materials from
environmental and occupational hazards. The skin permeability of industrial and
household chemicals plays an important role in various fields including toxicology and
risk assessment of hazardous materials, transdermal delivery of drugs and the plan of
cosmetic products [1]. In this work, a three-dimensional quantitative structure–activity
relationship (3DQSAR) model [2] has been developed to predict skin permeation of a
variety of 210 compounds through human skin. Molecular descriptors were computed
using GRid Independent Descriptors (GRIND) approach [3]. After variable selection via
genetic algorithm method, 100 selected descriptors were correlated with skin
permeability constants by various methods, such as PLS regression, support vector
machine (SVM), and so on. Therefore, compounds are separated in two classification:
150 molecules as set of training and other compounds as set of test. The best results
were obtained by PLS regression with the correlation coefficient of R2= 0.61 for
calibration set. This strategy led to a final QSAR model that presented Q2= 0.59 and
R2
pred=0.64 . As a result, the hydrogen bonding donor and hydrogen bonding acceptor of
investigated compounds greatly influences their ability to penetrate through human skin.
Furthermore, it has been observed that permeability was enhanced by increasing
hydrophobicity and decreasing molecular weight.