Antiproliferative and protein kinase binding activities of Some N6, 5'-bis-ureido 5'-amino-5'-deoxyadenosine derivatives.
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.
Peterson
Matt A
MA
Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, USA. matt_peterson@byu.edu
Oliveira
Marcelio
M
Christiansen
Michael A
MA
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003839:Deoxyadenosines / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D047428:Protein Kinase Inhibitors; C057928:5'-amino-5'-deoxyadenosine; D011494:Protein Kinases