Structure-based virtual screening for plant-based ERbeta-selective ligands as potential preventative therapy against age-related neurodegenerative diseases.
ERbeta has been associated with estrogen-induced promotion of memory function and neuronal survival. Based on the optimized complex structure of human ERbeta LBD bound with genistein, computer-aided structure-based virtual screening against a natural source chemical database was conducted to determine the occurrence of plant-based ERbeta-selective ligands. Twelve representative hits derived from database screening were assessed for their binding profiles to both ERs, three of which displayed over 100-fold binding selectivity to ERbeta over ERalpha.
Zhao
Liqin
L
Department of Molecular Pharmacology & Toxicology and the Program in Neuroscience, School of Pharmacy, University of Southern California, Los Angeles, California 90089, USA.
Brinton
Roberta D
RD
D000375:Aging; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry; D001665:Binding Sites; D001667:Binding, Competitive; D016208:Databases, Factual; D047628:Estrogen Receptor alpha / Q000737:chemistry; D047629:Estrogen Receptor beta / Q000737:chemistry*; D005454:Fluorescence Polarization; D019833:Genistein / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry; D048789:Phytoestrogens / Q000138:chemical synthesis* / Q000737:chemistry; D010944:Plants / Q000737:chemistry*; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship
D001578:Benzopyrans; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D018696:Neuroprotective Agents; D048789:Phytoestrogens; D019833:Genistein