The molecular docking followed by comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) was employed to the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of estrogen receptor-β of 33 quinoline derivatives. A significant correlation coefficient was obtained between total scores and binding affinities. The results showed that the hydrogen-bonding interactions between the hydroxy group of chromane and quinoline ring and the receptor, hydrophobic interactions between the ligand and the active site of estrogen receptor-β, and electronic interactions between the ligand and the Arg346 and Glu305 residuals were the dominant factors affecting the binding affinities. Besides, the steric effect of substituting group of quinoline ring also affected the binding activities. Based on the docking conformations, CoMFA and CoMSIA were employed to the QSAR studies of 33 quinoline derivatives. The number of principal components, r2, q2 (leave-one-out, LOO), of the optimal CoMSIA model were 6, 0.958, 0.669 and 0.741 respectively. The conclusions obtained from contour map analysis were in agreement with the docking results.

Key words: QSAR, CoMFA, CoMSIA, molecular docking, quinoline, estrogen receptor-β