Prediction of anticancer molecules using hybrid model developed on molecules screened against NCI-60 cancer cell lines

In past, numerous quantitative structure-activity relationship (QSAR) based models have been developed for predicting anticancer activity for a specific class of molecules against different cancer drug targets. In contrast, limited attempt have been made to predict the anticancer activity of a diverse class of chemicals against a wide variety of cancer cell lines. In this study, we described a hybrid method developed on thousands of anticancer and non-anticancer molecules tested against National Cancer Institute (NCI) 60 cancer cell lines.

Our analysis of anticancer molecules revealed that majority of anticancer molecules contains 18–24 carbon atoms and are dominated by functional groups like R₂NH, R₃N, ROH, RCOR, and ROR. It was also observed that certain substructures (e.g., 1-methoxy-4-methylbenzene, 1-methoxy benzene, Nitrobenzene, Indole, Propenyl benzene) are more abundant in anticancer molecules. Next, we developed anticancer molecule prediction models using various machine-learning techniques and achieved maximum matthews correlation coefficient (MCC) of 0.81 with 90.40 % accuracy using support vector machine (SVM) based models. In another approach, a novel similarity or potency score based method has been developed using selected fragments/fingerprints and achieved maximum MCC of 0.82 with 90.65 % accuracy. Finally, we combined the strength of above methods and developed a hybrid method with maximum MCC of 0.85 with 92.47 % accuracy.

We developed a hybrid method utilizing the best of machine learning and potency score based method. The highly accurate hybrid method can be used for classification of anticancer and non-anticancer molecules. In order to facilitate scientific community working in the field of anticancer drug discovery, we integrate hybrid and potency method in a web server CancerIN. This server provides various facilities that includes; virtual screening of anticancer molecules, analog based drug design, and similarity with known anticancer molecules (http://​crdd.​osdd.​net/​oscadd/​cancerin).