Aromatase Inhibitors from Broussonetia papyrifera

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2001-10, Vol.64 (10), p.1286-1293
• Main Authors: LEE, Dongho, BHAT, Krishna P. L., FONG, Harry H. S., FARNSWORTH, Norman R., PEZZUTO, John M., KINGHORN, A. Douglas
• Format: Article
• Language: English
• Subjects: Algorithms; Anticarcinogenic Agents - chemistry; Anticarcinogenic Agents - isolation & purification; Anticarcinogenic Agents - pharmacology; Aromatase; Aromatase Inhibitors; Benzofurans - chemistry; Benzofurans - isolation & purification; Benzofurans - pharmacology; Biological and medical sciences; Chalcone - analogs & derivatives; Chalcone - chemistry; Chalcone - isolation & purification; Chalcone - pharmacology; Chalcones; Circular Dichroism; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Female; Flavanones; Flavonoids - chemistry; Flavonoids - isolation & purification; Flavonoids - pharmacology; General pharmacology; Humans; Illinois; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Microsomes - enzymology; Molecular Structure; Moraceae - chemistry; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Placenta - enzymology; Plants, Medicinal - chemistry; Pregnancy; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Structure-Activity Relationship; Terpenes - chemistry; Terpenes - isolation & purification; Terpenes - pharmacology
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np010288l

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.