Abstract
A series of emodin analogues have been demonstrated to exhibit potent antiproliferative activity in three human epidermal growth factor receptor 2 (HER2)‑overexpressing cell lines. However, in docking simulations, not all of these emodin analogues docked into the HER2 protein binding site. As the epidermal growth factor receptor (EFGR) and HER2 proteins are members of the ErbB family, the present study aimed to determine whether these anthraquinone derivatives exhibit potent antitumour bioactivity due to their inhibition of EGFR protein. Two 2D quantitative structure‑activity relationship (QSAR) models, applied using multiple linear regression and a support vector machine, indicated seven representative molecular descriptors of anthraquinone derivatives associated with their antitumour activities. Molecular docking simulation indicated the possible docking poses of binding in the EGFR kinase domain. Two 3D‑QSAR models performed by comparative force field analysis and comparative similarity indices analysis indicated the favoured and disfavoured fields for four physicochemical parameters (steric and hydrophobic properties, and hydrogen bond donor and acceptor), which may further improve the antitumour properties. These results demonstrate the benefits of further investigations on the development of lead compounds with improved anticancer bioactivity.