New potential antitumor compounds from the plant Aristolochia manshuriensis as inhibitors of the CDK2 enzyme.
The 70% aqueous methanolic extract of the Chinese plant Aristolochia manshuriensis was found to contain two novel substituted phenanthrene compounds, SCH 546909 (1), and another phenanthrene glycoside (2). The structures of 1 and 2 were established based on NMR studies. They were identified as inhibitors of the CDK2 enzyme. Compound 1 was found to be a potent inhibitor of the CDK2 enzyme with an IC50 of 140 nM, whereas compound 2 was found to be less active with an IC50 of >10 microM.
Hegde
Vinod R
VR
Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. vinod.hegde@spcorp.com
Borges
Scott
S
Patel
Mahesh
M
Das
Pradip R
PR
Wu
Bonnie
B
Gullo
Vincent P
VP
Chan
Tze-Ming
TM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D030022:Aristolochia / Q000737:chemistry*; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006027:Glycosides / Q000737:chemistry* / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000737:chemistry; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D006027:Glycosides; D006576:Heterocyclic Compounds, 4 or More Rings; D010936:Plant Extracts; C549644:SCH 546909; D014867:Water; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D000432:Methanol