Prenylflavonoids: a new class of non-steroidal phytoestrogen (Part 1). Isolation of 8-isopentenylnaringenin 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 Anaxagorea luzonensis A. Gray (Annonaceae), resulted in the isolation of 8-isopentenylnaringenin (1) as an estrogen agonist with a 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.
Kitaoka
M
M
Exploratory Chemistry Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo, Japan.
Kadokawa
H
H
Sugano
M
M
Ichikawa
K
K
Taki
M
M
Takaishi
S
S
Iijima
Y
Y
Tsutsumi
S
S
Boriboon
M
M
Akiyama
T
T
D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D008518:Medicine, East Asian Traditional; D015394:Molecular Structure; D048789:Phytoestrogens; D010936:Plant Extracts / Q000737:chemistry; D028321:Plant Preparations; D010946:Plants, Medicinal; D011959:Receptors, Estradiol / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013785:Thailand; D014407:Tumor Cells, Cultured
C114744:8-isopentenylnaringenin; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D010936:Plant Extracts; D028321:Plant Preparations; D011959:Receptors, Estradiol; D004958:Estradiol; D019833:Genistein