Bioassay-guided fractionation of a methanolic extract of a Thai crude drug, derived
from heartwood of Anaxagorea luzonensis A. Gray (Annonaceae), resulted in the isolation of 8-isopentenylnaringenin (1) as an estrogen agonist with an activity of about an order of magnitude greater than
genistein. Various flavonoids possessing isopentenyl side chains in the A-ring have
been prepared and evaluated for their ability to bind estrogen receptor. In addition,
enantiomers of 1 were separated and the respective enantiomers were assayed. These studies have demonstrated
that the presence of an 8-isopentenyl group is an important factor for binding. Flavones,
flavanones and flavonols having an isopentenyl substituent at C-8 exhibited an appreciable
affinity for estrogen receptor. Conversely, isoflavones possessing an 8-isopentenyl
substituent at C-8 did not show this activity. Movement of the isopentenyl group from
position 8 to 6 resulted in loss of the activity. No significant difference was observed
between 2(S)- and 2(R)-enantiomers of 1 in their binding affinity. Prenylflavonoids are reported to possess a wide range
of biological activities; however, estrogenic activity has not been described.
Anaxagorea luzonensis A. Gray - Annonaceae - prenylflavonoid - non-steroidal estrogen agonist - phytoestrogen
- isopentenylnaringenin - isopentenylapigenin
