Computational approaches to the prediction of the 1 - octanol / water partition coefficient of benzimidazole derivatives drugs

It is important to determine whether a candidate molecule is capable of penetrating the partition coefficient octanolwater (LogPo/w) in drug discovery and development. The aim of this paper is to establish a predictive model for LogPo/w penetration using simple descriptors. The usefulness of the quantum chemical descriptors, calculated at the level of the HF theory using 6-31+G** basis set for QSAR study of Benzimidazole derivatives was examined. The QSAR model developed contributed to a mechanistic understanding of the investigated biological effects. In this study was to use a dataset containing 38 drugs with known activity. A multiple linear regression (MLR) procedure was used to model the relationships between molecular descriptors and the partition coefficient (LogPo/w) of the Benz imidazole derivatives. The stepwise regression method was used to derive the most significant models as a calibration model for predicting the LogPo/w of this class of molecules. Biological activities contain the logarithm of the ratio of the steady-state concentration of a compound in the 1-octanol to in the water, log P. A multi-parametric equation containing maximum four descriptors at HF/6-31+G** method with good statistical qualities ( RMAX= 0 .911, R 2 MAX= 0.829 Q =0.6877at HF/631+G**) was obtained by Multiple Linear Regression using stepwise method. The best QSAR models were further validated by a leave one out technique as well as by the calculation of statistical parameters for the established theoretical models. To confirm the predictive power of the models, an external set of molecules was used. High agreement between experimental and predicted LogPo/w values, obtained in the validation procedure, indicated the good quality of the derived QSAR models.