Neda Ahmadinejad and Fatemeh Shafiei* Pages 387 - 399 ( 13 )
Aim and Objective: A Quantitative Structure-Activity Relationship (QSAR) has been widely developed to derive a correlation between chemical structures of molecules to their known activities. In the present investigation, QSAR models have been carried out on 76 Camptothecin (CPT) derivatives as anticancer drugs to develop a robust model for the prediction of physicochemical properties.
Materials and Methods: A training set of 60 structurally diverse CPT derivatives was used to construct QSAR models for the prediction of physiochemical parameters such as Van der Waals surface area (SvdW), Van der Waals Volume (VvdW), Molar Refractivity (MR) and Polarizability (α). The QSAR models were optimized using Multiple Linear Regression (MLR) analysis. A test set of 16 compounds was evaluated using the defined models.
The Genetic Algorithm And Multiple Linear Regression Analysis (GA-MLR) were used to select the descriptors derived from the Dragon software to generate the correlation models that relate the structural features to the studied properties.
Results: QSAR models were used to delineate the important descriptors responsible for the properties of the CPT derivatives. The statistically significant QSAR models derived by GA-MLR analysis were validated by Leave-One-Out Cross-Validation (LOOCV) and test set validation methods. The multicollinearity and autocorrelation properties of the descriptors contributed in the models were tested by calculating the Variance Inflation Factor (VIF) and the Durbin–Watson (DW) statistics.
Conclusion: The predictive ability of the models was found to be satisfactory. Thus, QSAR models derived from this study may be helpful for modeling and designing some new CPT derivatives and for predicting their activity.
Camptothecin (CPT) derivatives, QSAR, polarizability, GA-MLR, molecular descriptors, Leave-One-Out Cross- Validation, molar refractivity, van der Waals surface, van der Waals volume.
Department of Chemistry, Arak Branch, Islamic Azad University, Arak, Department of Chemistry, Arak Branch, Islamic Azad University, Arak