Structure-activity relationship study of rutaecarpine analogous active against central nervous system cancer

Abstract

In order to relate the geometric and electronic descriptors of the rutaecarpine analogous to their biological activity against cancer of the central nervous system (CNS), molecular quantum chemical calculations at B3LYP/6-31(d) level and statistical analysis were carried out for 21 rutaecarpine analogous. Out of the 86 molecular descriptors calculated, 5 were selected to build the principal component analysis (PCA) model. The PC1 component that accounts for 46.11% of the total variance of the data was alone able to discriminate completely the compounds into two classes: active and inactive. All molecular descriptors selected by PCA model are electronic parameters. The hierarchical cluster analysis (HCA) was also applied on the selected descriptors. Based on the 5 electronic descriptors selected, it is possible to suggest new compounds to be synthesized with activity against CNS cancer. In addition to that, a supervised partial least squares discriminant analysis (PLS-DA) model was built and successfully applied to discriminate rutaecarpine analogues, being validated through an independent test set and considered robust to overfitting. ©2012 Sociedade Brasileira de Química.