QSAR Prediction of the Penetration of Drugs Across a Polydimethylsiloxane Membrane
Weiping Ma, Feng Luan, Chunyan Zhao, Xiaoyun Zhang, Mancang Liu, Zhide Hu, Botao Fan · QSAR & Combinatorial Science · 2006
Abstract A quantitative structure–activity relationship was developed by the Heuristic Method (HM) to study the penetration of 245 drugs across a polydimethylsiloxane membrane. The descriptors in this study were calculated by the software CODESSA. HM was used both for preselecting molecular descriptors and for developing the linear model. Logarithms of the maximum steady‐state flux (J) values are correlated with four descriptors, with a squared correlation coefficient (R2) of 0.844 and root‐mean‐square error of 0.438, respectively. These four theoretical molecular descriptors are count of H‐acceptor sites, gravitation index, H‐donors charged surface area, and weighted positive‐charged partial surface area. The rationality of the descriptors was evaluated by similarity analysis, while the stability and validity of the model was evaluated by validation. This paper provides a simple and straightforward way to predict the log J values of the drugs from their structures alone and gives some insight into structural features related to the penetration of drugs.