Antiproliferative and protein kinase binding activities of Some N6, 5'-bis-ureido 5'-amino-5'-deoxyadenosine derivatives.

Abstract

Two novel N(6),5'-bis-ureido 5'-amino-5'-deoxyadenosine derivatives are shown to inhibit tumor cell growth in the NCI 60 human tumor cell panel. Compounds 2c and 2d exhibited GI(50) values of 1-6 microM in 35 and 14 cell lines, respectively. Compound 2c was shown to selectively inhibit binding of protein kinases to immobilized ATP-binding site ligands via a competitive binding assay (11 of 353 protein kinases inhibited by > or =30% at 10 microM compound concentration). Enzyme inhibition assays revealed modest inhibition for PAK4 and FMS (21 and 17%, respectively). A brief SAR study suggests that a 2'-O-TBDMS is necessary for antiproliferative activity.

• Authors: Matt A Peterson, Marcelio Oliveira, Michael A Christiansen
• Journal: Nucleosides, nucleotides & nucleic acids (Nucleosides Nucleotides Nucleic Acids) Vol. 28 Issue 5 Pg. 394-407 (May 2009) ISSN: 1532-2335 [Electronic] United States
• PMID: 20183591 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Deoxyadenosines
• Protein Kinase Inhibitors
• 5'-amino-5'-deoxyadenosine
• Protein Kinases

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Deoxyadenosines (chemistry, pharmacology)
• Drug Screening Assays, Antitumor
• Humans
• Protein Binding
• Protein Kinase Inhibitors (chemistry, pharmacology)
• Protein Kinases (metabolism)