CHED 1320 |
| Histone deacetylase inhibitors have been studied extensively in the treatment of cancer due to their ability to induce growth arrest, differentiation, and apoptosis in cancer cells. The proposed histone deacetylase inhibitor is a three-part pharmacophore that includes the cap group, which binds to the outer rim of the active site, the zinc chelator, which binds to the zinc cation located within the active site, and the linker chain, a hydrophobic spacer that spans the membrane and connects the cap group to the zinc chelator. A target molecule has been designed through computational analysis indicating that; an isatin moiety binds specifically to the outer rim of the active site, a six carbon chain linker sufficiently spans the cavity, and the hydroxamic acid moiety is a powerful zinc chelator. Lowrie has outlined the synthesis of isatin beginning with a phenylhydrazone. Giacomelli et al. have developed a high-yielding synthesis of a hydroxamic acid from a carboxylic acid. These methods have been adapted in order to synthesize the target molecule. In order to proceed with the isatin synthesis, a phenylhydrazone has been produced. The ester portion of the isatin product will be converted to a carboxylic acid through acid hydrolysis. The carboxylic acid will then be converted to hydroxamic acid. Products will be verified with infrared spectroscopy, mass spectrometry, and melting point determinations. |
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Undergraduate Research Poster Session: Medicinal Chemistry
2:00 PM-4:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Poster
Division of Chemical Education |