Screening of herbal constituents for aromatase inhibitory activity

• Published in: Bioorganic & medicinal chemistry 2008-09, Vol.16 (18), p.8466-8470
• Main Authors: Paoletta, S., Steventon, G.B., Wildeboer, D., Ehrman, T.M., Hylands, P.J., Barlow, D.J.
• Format: Article
• Language: English
• Subjects: Algorithms; Aminoglutethimide - pharmacology; Aromatase; Aromatase Inhibitors - pharmacology; Biological and medical sciences; CYP19; Cytochrome P450; Docking; Drug Evaluation, Preclinical - methods; Drugs, Chinese Herbal - pharmacology; Flavanones - pharmacology; Flavonoids - pharmacology; Fluorometry; General pharmacology; Gossypetin; Humans; Inhibitory Concentration 50; Liquiritigenin; Medical sciences; Models, Molecular; Myricetin; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Random Forests; Structure-Activity Relationship; Traditional Chinese medicine
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2008.08.034

Random Forest screening of the phytochemical constituents of 240 herbs used in traditional Chinese medicine identified a number of compounds as potential inhibitors of the human aromatase enzyme (CYP19). Molecular modelling/docking studies indicated that three of these compounds (myricetin, liquiritigenin and gossypetin) would be likely to form stable complexes with the enzyme. The results of the virtual screening studies were subsequently confirmed experimentally, by in vitro (fluorimetric) assay of the compounds’ inhibitory activity. The IC-50s for the flavones, myricetin and gossypetin were determined as 10 and 11 μM, respectively, whilst the flavanone, liquiritigenin, gave an IC-50 of 0.34 μM—showing about a 10-fold increase in potency, therefore, over the first generation aromatase inhibitor, aminoglutethimide.