A 3D-QSAR-based interaction analysis of Quinazoline derivatives for promising antitumor activity

Abstract Quinazoline compounds have significant scientific implications and can be employed as tyrosine kinase inhibitors to treat cancer. A reasonable three-dimensional quantitative conformational relationship (3D-QSAR) model for quinazoline compounds was constructed using comparative molecular analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) methods in order to obtain quinazoline compounds with good anti-tumor activity. The outcomes demonstrate the strong predictability and stability of the CoMFA and CoMSIA models(CoMFA: q 2 = 0.752,r 2 = 0.990,SEE = 0.098, F = 322.061; CoMSIA: q 2 = 0.748, r 2 = 0.991, SEE = 0.095, F = 286.959). The anti-tumor activity of the compound is benefited by the presence of large and hydrophilic negatively charged groups at the R, R 3 -position substitution site, according to the 3D-QSAR model analysis. The anti-tumor activity of the compound can also be enhanced by the presence of small volume hydrogen bonding receptor groups at the substitution sites of positions R 1 and R 2 . Furthermore, hydrophobicity at position R 1 is more beneficial, while hydrophobicity at position R 2 is the opposite. The 3D-QSAR research results offer some theoretical groundwork for future structural modifications of Quinazoline molecules.