Predicting Antitumor Activity of Anthrapyrazole Derivatives using Advanced Machine Learning Techniques.

Background: Anthrapyrazoles are a new class of antitumor agents and successors to anthracyclines possessing a broad range of antitumor activity in various model tumors.

Objectives: The present study introduces novel QSAR models for the prediction of antitumor activity of anthrapyrazole analogues.

Methods: The predictive performance of four machine learning algorithms, namely artificial neural networks, boosted trees, multivariate adaptive regression splines, and random forest, was studied in terms of variation of the observed and predicted data, internal validation, predictability, precision, and accuracy.

Results: ANN and boosted trees algorithms met the validation criteria. It means that these procedures may be able to forecast the anticancer effects of the anthrapyrazoles studied. Evaluation of validation metrics, calculated for each approach, indicated the artificial neural network (ANN) procedure as the algorithm of choice, especially with regard to the obtained predictability as well as the lowest value of mean absolute error. The designed multilayer perceptron (MLP)-15-7-1 network displayed a high correlation between the predicted and the experimental pIC₅₀ value for the training, test, and validation set. A conducted sensitivity analysis enabled an indication of the most important structural features of the studied activity.

Conclusion: The ANN strategy combines topographical and topological information and can be used for the design and development of novel anthrapyrazole analogues as anticancer molecules.