Descriptor analysis of estrogen receptor beta-selective ligands using 2-phenylquinoline, tetrahydrofluorenone and 3-hydroxy 6H-benzo[c]chromen-6-one scaffolds

作者：Balaji; Muthiah Ramanathan^*; Sabarinath; Ramamurthy; Chandrasekharan

来源：Journal of Enzyme Inhibition and Medicinal Chemistry, 2011, 26(6): 831-842.

DOI：10.3109/14756366.2011.566219

• Estrogen
• ER alpha and beta receptors
• anti-cancer
• phenylquinoline
• tetrahydrofluorenone
• 3-hydroxy-6H-benzo[c]chromen-6-one

Estrogen receptor beta (ER beta) selective ligands have attracted much attention recently in the design of anti-cancer drugs that are devoid of the common side effects of estrogen. Structural studies of estrogen receptor alpha (ER alpha) and beta revealed that there were considerable differences in their ligand-binding cavity and in their volume. Hence, the present study has hypothesized that size and shape descriptors can influence the affinity/selectivity of the ligands towards ER beta. To prove the same, quantitative structure-activity relationship (QSAR) analyses were carried out using multiple regression analysis on 2-phenylquinoline, tetrahydrofluorenone and 3-hydroxy-6H-benzo[c]chromen-6-one series. Results indicate that increased lipophilicity, decrease in ellipsoidal volume and width of substituents, presence of halogen atoms was essential for the ligands to have high affinity/selectivity towards ER beta. QSAR models obtained were both internally and externally validated. The study delineates that the size and shape descriptors are best modulators of ER beta affinity/selectivity. Docking studies were performed to support our QSAR results.

• 出版日期2011-12