ORGN 642 |
| Amamistatins A and B, isolated from an actinomycete, show anti-proliferative effects against human tumor cell lines and cytotoxicity against mouse lymphocytic leukemia cells. While their mode of action has not been determined, these compounds may be acting as histone deacetylase (HDAC) inhibitors via an ε-N-hydroxy-ε-N-acyl-lysine moiety. The amamistatins are also structurally similar to mycobactins, siderophores secreted by mycobacteria that have been investigated as anti-tuberculosis agents through interference with iron transport. Amamistatin B and a series of analogs with changes in metal binding ability and stereochemistry are being constructed via the synthesis of four key fragments. Amamistatin B, analogs, and synthetic intermediates are being tested for growth inhibitory activity against both PC-3 (prostate cancer) cells and M. tuberculosis H37Rv in order to determine the structural features that contribute to activity against each biological target.
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Proteins, Peptides, Amino Acids, and Enzyme Inhibitors
8:00 AM-12:00 PM, Thursday, 30 March 2006 Georgia World Congress Center -- C301, Oral
Division of Organic Chemistry |
