QSAR, human hepatocellular carcinoma anticancer screening, docking studies and in silico prediction of some N-(substituted)-9-alkyl-1- substituted-9H-β-carboline-3-carboxamide derivatives

Abstract

A quantitative structure activity relationship (QSAR) model for a series of β- carboline derivatives having human hepatocellular carcinoma inhibitory activities as effective anticancer agents was developed by the multiple linear regressions (MLR) method. In this study, the compounds were used in the model development were divided into a set of fifteen compounds as training set and set of four compounds as test set. A model with high prediction ability and high correlation coefficients was obtained. This model showed r = 0.9760, r2 = 0.9530 and Q2 = 0.903, the QSAR model was also employed to predict the experimental compounds in an external test set, and to predict the activity of a new designed set of N-(2-amino-2-substitutedethyl)-9-(substituted)-6 substituted-1- substituted- 9H-β- carboline-3 carboxamide derivatives (M1-M50), result showed that compound M30 has the most promising inhibition activity (pIC50 = 11.6455) against human hepatocellular carcinoma cell line (Bel7402). Besides, the model showed good correlative and predictive ability. The Docking studies show that compound M12 and M19 have the highest binding scores -9.7602 and -9.1456 kcal/mol respectively.