Diarylheptanoids, new phytoestrogens from the rhizomes of Curcuma comosa: Isolation, chemical modification and estrogenic activity evaluation.
Three new diarylheptanoids, a 1:2 mixture of (3S)- and (3R)-1-(4-methoxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol (13a and 13b) and 1-(4-hydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-one (15), together with two synthetically known diarylheptanoids 1,7-diphenyl-(1E,3E,5E)-1,3,5-triene (9) and 1-(4-hydroxyphenyl)-7-phenyl-(4E,6E)-4,6-heptadien-3-one (16), and nine known diarylheptanoids, 2, 8, 10-12, 14, a 3:1 mixture of 17a and 17b, and 18, were isolated from the rhizomes of Curcuma comosa Roxb. The absolute stereochemistry of the isolated compounds has also been determined using the modified Mosher's method. The isolated compounds and the chemically modified analogues were evaluated for their estrogenic-like transcriptional activity using RT-PCR in HeLa cell line. Some of the isolated diarylheptanoids and their modified analogues exhibited estrogenic activity comparable to or higher than that of the phytoestrogen genistein. Based on the transcriptional activation of both estrogenic targets, Bcl-xL and ERbeta gene expression, the structural features for a diarylheptanoid to exhibit high estrogenic activity are the presence of an olefinic function conjugated with the aromatic ring at the 7-position, a keto group at the 3-position, and a phenolic hydroxyl group at the p-position of the aromatic ring attached to the 1-position of the heptyl chain.
Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand. s_apichart@ru.ac.th
Apichart
A
Suksamrarn
Mathurose
M
Ponglikitmongkol
Kanjana
K
Wongkrajang
Anon
A
Chindaduang
Suthadta
S
Kittidanairak
Aroon
A
Jankam
Boon-ek
BE
Yingyongnarongkul
Narin
N
Kittipanumat
Ratchanaporn
R
Chokchaisiri
Pichit
P
Khetkam
Pawinee
P
Piyachaturawat
D030024:Curcuma / Q000737:chemistry*; D036381:Diarylheptanoids / Q000302:isolation & purification / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000235:genetics; D004967:Estrogens / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D048789:Phytoestrogens / Q000302:isolation & purification / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027343:Rhizome / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects; D051020:bcl-X Protein / Q000235:genetics
C494811:BCL2L1 protein, human; D036381:Diarylheptanoids; D047629:Estrogen Receptor beta; D004967:Estrogens; D048789:Phytoestrogens; D051020:bcl-X Protein