Research Abstracts Online
January 2009 - March 2010
University of Minnesota Twin Cities
Academic Health Center
Center for Drug Design
PI: Krzysztof W. Pankiewicz
Novel tiazofurin adenine dinucleotide (TAD) analogues containing a substituent at the C2 of adenine ring have been synthesized as inhibitors of the two isoforms of human IMP-dehydrogenase. The 2-ethyl TAD analogue was found to be the most potent. It did not inhibit other cellular dehydrogenases up to 50 µM. Mycophenolic adenine bis(phosphonate)s containing the 2-phenyl and 2-ethyl group were prepared as metabolically stable compounds, both nanomolar inhibitors. These compounds inhibited proliferation of leukemic K562 cells more potently than tiazofurin or mycophenolic acid. The researchers are using the BMSDL for this project.
Krzysztof Felczak, Research Associate