PRENYLFLAVONOIDS - A NEW CLASS OF NONSTEROIDAL PHYTOESTROGEN (PART 1)- ISOLATION OF 8-LSOPENTENYLNARINGENIN AND AN INITIAL STUDY ON ITS STRUCTURE-ACTIVITY RELATIONSHIP

Bioassay-guided fractionation of a methanolic extract of a Thai crude drug, derived from heartwood of Anaxogorea luzonensis A. Gray (Annonac eae), resulted in the isolation of 8-isopentenylnaringenin (1) as an e strogen agonist with an activity of about an order of magnitude greate r than genistein. Various flavonoids possessing isopentenyl side chain s in the A-ring have been prepared and evaluated for their ability to bind estrogen receptor. In addition, enantiomers of 1 were separated a nd the respective enantiomers were assayed. These studies have demonst rated that the presence of an 8-isopentenyl group is an important fact or for binding. Flavones, flavanones and flavonols having an isopenten yl substituent at C-8 exhibited an appreciable affinity for estrogen r eceptor. Conversely, isoflavones possessing an 8-isopentenyl substitue nt at C-8 did not show this activity. Movement of the isopentenyl grou p from position 8 to 6 resulted in loss of the activity. No significan t difference was observed between 2(S)- and Z(R)-enantiomers of 1 in t heir binding affinity. Prenylflavonoids are reported to possess a wide range of biological activities: however, estrogenic activity has not been described.