Establishment of the quantitative structure-activity relationship between the structure of terpenoids and their enhancing drug penetration ability through human skin based on density functional theory / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish the quantitative structure-activity relationship (QSAR) for predicting the percutaneous permeation enhancing activity of terpenoids, using the indexes of reactivity in molecules as the important descriptors. METHODS: The structural and thermodynamic parameters of 41 terpenoids were optimized using B3/LYP method of DFT at the level of 6-311 + + G (2d, p). The backward method in stepwise multiple regression was used to establish the QSAR model for predicting activities of terpenes that enhanced drug penetration through human skin. RESULTS: The multiple correlation coefficient (r) was determined to be 0.655 and the square cross validated correlation coefficient (RCV2) was determined to be 0. 654. The QSAR model indicated that the electrostatic potentials (VS,ta, VS,max, VS,min), chemical potential (X), thermal capacity (Cp), and dipole moment (D) of individual molecules could be responsible for the in vitro permeation enhancing abilities of terpenoids. CONCLUSION: The indexes of reactivity in molecules based on density functional theory can simulate more exactly the quantitative relationship between the structures of penetration enhancers and their percutaneous permeation enhancing abilities for drugs, which will facilitate reasonable explanation of the model.