Aromatase inhibitors from Broussonetia papyrifera.
Bioassay-guided fractionation of an ethyl acetate-soluble extract from the whole plants of Broussonetia papyrifera, using an in vitro aromatase inhibition assay, led to the isolation of five new active compounds, 5,7,2',4'-tetrahydroxy-3-geranylflavone (1), isogemichalcone C (8), 3'-[gamma-hydroxymethyl-(E)-gamma-methylallyl]-2,4,2',4'-tetrahydroxychalcone 11'-O-coumarate (9), demethylmoracin I (10), and (2S)-2',4'-dihydroxy-2' '-(1-hydroxy-1-methylethyl)dihydrofuro[2,3-h]flavanone (11), and 10 known (12-21) compounds which were also found to be active. Of these compounds, the most potent were 9 (IC(50) 0.5 microM), 11 (IC(50) 0.1 microM), isolicoflavonol (12, IC(50) 0.1 microM), and (2S)-abyssinone II (13, IC(50) 0.4 microM). Additionally, six new compounds, 5,7,3',4'-tetrahydroxy-6-geranylflavonol (2), 5,7,3',4'-tetrahydroxy-3-methoxy-6-geranylflavone (3), (2S)-7,4'-dihydroxy-3'-prenylflavan (4), 1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)propane (5), 1-(2,4-dihydroxy-3-prenylphenyl)-3-(4-hydroxyphenyl)propane (6), and 1-(4-hydroxy-2-methoxyphenyl)-3-(4-hydroxy-3-prenylphenyl)propane (7), were isolated and characterized, but proved to be inactive as aromatase inhibitors, as were an additional 21 known compounds. The structures of the new compounds (1-11) were elucidated by spectroscopic methods. Structure-activity relationships in the aromatase assay were determined for the benzofurans, biphenylpropanoids, coumarins, and various types of flavonoids (chalcones, flavans, flavanones, and flavones) obtained among a total of 42 constituents of B. papyrifera.
Lee
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Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
Bhat
K P
KP
Fong
H H
HH
Farnsworth
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NR
Pezzuto
J M
JM
Kinghorn
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AD
D000465:Algorithms; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001141:Aromatase; D047072:Aromatase Inhibitors; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002599:Chalcone / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D047188:Chalcones; D002942:Circular Dichroism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005260:Female; D044950:Flavanones; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D007087:Illinois; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008861:Microsomes / Q000201:enzymology; D015394:Molecular Structure; D029586:Moraceae / Q000737:chemistry*; D010920:Placenta / Q000201:enzymology; D010946:Plants, Medicinal / Q000737:chemistry; D011247:Pregnancy; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
C439983:2',4'-dihydroxy-2''-(1-hydroxy-1-methylethyl)dihydrofuro(2,3-h)flavanone; C439980:3'-hydroxymethylmethylallyl-2,4,2',4'-tetrahydroxychalcone 11'-O-coumarate; C439977:5,7,2',4'-tetrahydroxy-3-geranylflavone; D016588:Anticarcinogenic Agents; D047072:Aromatase Inhibitors; D001572:Benzofurans; D047188:Chalcones; D004791:Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D013729:Terpenes; C439981:demethylmoracin I; C439979:isogemichalcone C; D002599:Chalcone; D001141:Aromatase