An attempt has been made for the development of quantitative structure-activity relationship (QSAR) models for a series of β-carboline derivatives having DYRK1A (dual specificity tyrosine phosphorylated and regulated kinase 1a) inhibitory activities as potent anticancer agents toward the activation of caspase-9 which leads to massive apoptosis in different human cancer cell types including glioma, esophageal cancer and non-small-cell lung cancers respectively. A number of highly descriptive and predictive QSAR models for these compounds were obtained by considering in vitro anticancer activities against glioma cell lines including U373 and Hs683 respectively with various sets of theoretical molecular descriptors including topological, constitutional, geometrical, functional groups and atom centered fragment indices calculated solely from the structures of 48 synthesized β-carboline derivatives using stepwise-multiple linear regressions methods. Model validation is performed by incorporating training and test sets approach and calculating R2, QLoo2, Rpred2 and standard error of estimation (SEE) respectively. From these models a number of significant features of these congeners including X3Av, EEig13x, MATS5m and SP05 which are responsible for size, shape and weight of the molecules whereas EEig03d, MATS4p and QYYp which indicate dipole moment, polarizabilities, conjugation and aromaticity have been predicted for the design of more promising β-carboline anticancer compounds.
