Comparative QSAR Modeling For Predicting Anticancer Potency of Imidazo[4,5-B]Pyridine Derivatives Using GA-MLR and BP-ANN Techniques



Prediction of toxicity of imidazo[4,5-b]pyridine derivatives is carried out using GA-MLR and BPANN methods.



A quantitative structure-property relationship (QSPR) was determined based on methods, including genetic algorithm-multiple linear regression (GA-MLR) and backpropagation artificial neural network (BP-ANN). These methods were employed for modeling and predicting the anticancer potency of imidazo[4,5-b]pyridine derivatives.



A dataset of imidazo[4,5-b]pyridine derivatives was randomly divided into two groups, training and test sets consisting of 75% and 25% of data points, respectively. The optimized conformation of compounds was obtained using the DFT-B3LYP method and 6-31G* basis sets level with Gaussian 09 software. A large number of molecular descriptors were calculated using Dragon software. The QSAR models were optimized using multiple linear regressions (MLR).



The most relevant molecular descriptors were obtained using the genetic algorithm (GA) and backward stepwise regression. The predictive powers of the GA-MLR models were studied using leave-one-out (LOO) cross-validation and an external test set.



The obtained results of statistical parameters showed the BP-ANN model to have better performance compared to the GA-MLR model.
To assess the predictive ability of QSAR models, many statistical terms, such as correlation coefficient (R2), leave-one-out cross-validation (LOOCV), root mean squared error (RMSE), and external and internal validation were used. The results of validation methods demonstrate the QSAR model to be robust and with high predictivity.
