Screening of herbal constituents for aromatase inhibitory activity.
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 microM, respectively, whilst the flavanone, liquiritigenin, gave an IC-50 of 0.34 microM--showing about a 10-fold increase in potency, therefore, over the first generation aromatase inhibitor, aminoglutethimide.
Paoletta
S
S
Pharmaceutical Science Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE19NH, United Kingdom.
Steventon
G B
GB
Wildeboer
D
D
Ehrman
T M
TM
Hylands
P J
PJ
Barlow
D J
DJ
D000465:Algorithms; D000616:Aminoglutethimide / Q000494:pharmacology; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D044950:Flavanones / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005470:Fluorometry; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D047072:Aromatase Inhibitors; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D005419:Flavonoids; D000616:Aminoglutethimide; C040015:myricetin; C059922:gossypetin; C083152:liquiritigenin; C028610:flavanone