A new dimeric dihydrochalcone and a new prenylated flavone from the bud covers of Artocarpus altilis: potent inhibitors of cathepsin K.
A MeOH/CH(2)Cl(2) extract of the bud covers of Artocarpus altilis collected in Micronesia showed activity in a cathepsin K inhibition assay. In addition to the three known flavonoids isolated from the bud covers of this species, two new compounds have been identified whose structures were determined on the basis of spectral data. These compounds include a dimeric dihydrochalcone, cycloaltilisin 6 (2), and a new prenylated flavone, cycloaltilisin 7 (3). Novel compounds 2 and 3 have IC(50) values of 98 and 840 nM, respectively, in cathepsin inhibition.
Patil
Ashok D
AD
Drug Discovery, Millennium Pharmaceuticals Inc., 75-5 Sidney Street, Cambridge, Massachusetts 02139, USA.
Freyer
Alan J
AJ
Killmer
Lew
L
Offen
Priscilla
P
Taylor
Paul B
PB
Votta
Bartholomew J
BJ
Johnson
Randall K
RK
D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D002599:Chalcone / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008849:Micronesia; D015394:Molecular Structure; D029586:Moraceae / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010946:Plants, Medicinal; D013055:Spectrophotometry, Infrared
D015853:Cysteine Proteinase Inhibitors; D005419:Flavonoids; C457256:cycloaltilisin 6; C457257:cycloaltilisin 7; D002599:Chalcone; D002403:Cathepsins; D056657:Cathepsin K