New potential antitumor compounds from the plant Aristolochia manshuriensis as inhibitors of the CDK2 enzyme

Vinod R Hegde; Scott Borges; Mahesh Patel; Pradip R Das; Bonnie Wu; Vincent P Gullo; Tze-Ming Chan

doi:10.1016/j.bmcl.2010.01.018

New potential antitumor compounds from the plant Aristolochia manshuriensis as inhibitors of the CDK2 enzyme

Bioorg Med Chem Lett. 2010 Feb 15;20(4):1344-6. doi: 10.1016/j.bmcl.2010.01.018. Epub 2010 Jan 11.

Authors

Vinod R Hegde¹, Scott Borges, Mahesh Patel, Pradip R Das, Bonnie Wu, Vincent P Gullo, Tze-Ming Chan

Affiliation

¹ Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. vinod.hegde@spcorp.com

PMID: 20097074
DOI: 10.1016/j.bmcl.2010.01.018

Abstract

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.

MeSH terms

Antineoplastic Agents / pharmacology*
Aristolochia / chemistry*
Cyclin-Dependent Kinase 2 / antagonists & inhibitors*
Drugs, Chinese Herbal / chemistry
Drugs, Chinese Herbal / pharmacology
Enzyme Activation / drug effects
Glycosides / chemistry*
Glycosides / pharmacology
Heterocyclic Compounds, 4 or More Rings / chemistry*
Heterocyclic Compounds, 4 or More Rings / pharmacology
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy
Methanol / chemistry
Molecular Structure
Plant Extracts / chemistry*
Water / chemistry

Substances

Antineoplastic Agents
Drugs, Chinese Herbal
Glycosides
Heterocyclic Compounds, 4 or More Rings
Plant Extracts
SCH 546909
Water
CDK2 protein, human
Cyclin-Dependent Kinase 2
Methanol