In vitro and in silico perspectives on estrogenicity of tanshinones from Salvia miltiorrhiza.
This work aims to investigate the structure-activity relationship for binding and activation of human estrogen receptor α ligand binding domain (hERα-LBD) with tanshinones by a combination of in vitro and in silico approaches. The recombinant hERα-LBD was expressed in E. coli strain. The direct binding interactions of tanshinones with hERα-LBD and their ERα agonistic potency were investigated by fluorescence polarization (FP) and reporter gene assays, respectively. FP assay suggested that the tested tanshinones can bind to hERα-LBD as affinity ligands. Tanshinones acted as agonists of hERα as demonstrated by transactivation of estrogen response element (ERE) in transiently transfected MCF-7 cells and by molecular docking of these compounds into the hydrophobic binding pocket of hERα-LBD. Interestingly, comparison of the calculated binding energies versus Connolly solvent-excluded volume and experimental binding affinities showed a good correlation. This work may provide insight into chemical and pharmacological characterization of novel bioactive compounds from Salvia miltiorrhiza.
['Zhang|Tiehua|T|', 'Zhong|Shuning|S|', 'Wang|Yongjun|Y|', 'Dong|Shuyue|S|', 'Guan|Tianzhu|T|', 'Hou|Ligang|L|', 'Xing|XiaoJia|X|', 'Zhang|Jie|J|', 'Li|Tiezhu|T|']
D045784:Abietanes D004926:Escherichia coli D004965:Estrogen Antagonists D004967:Estrogens D006801:Humans D062105:Molecular Docking Simulation D027561:Salvia miltiorrhiza
Tanshinones Fluorescence polarization Molecular docking Estrogenic activity Luciferase reporter assay