CARB 95 |
| The anthracycline antibiotics daunorubicin and doxorubicin are widely used anticancer agents. The clinical value of both agents is limited, however, by an unusual cardiomyopathy and the development of multidrug resistance (MDR). To identify new anticancer agents with novel biological properties, we have developed a modular approach to the design of DNA-binding agents. The design is based in part on the availability of unique carbohydrate moiety-based minor groove-binding building blocks that can be used to create libraries of DNA binders. We have synthesized a series of novel carbohydrates with an L-configuration that are mono- and difluorinated at C-4 and C-6 and prepare useful glycosyl donors. The value of our approach has been demonstrated by coupling these novel carbohydrate-based building blocks with intercalators like daunomycinone and adriamycinone and subsequent assessment of their activity in vivo. Prepared compounds, selected structures of which are shown below, were more potent than the parent drugs, and some compounds were highly active against MDR tumor cell lines.
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Nucleic Acid Therapeutics
9:00 AM-11:45 AM, Wednesday, March 28, 2007 McCormick Place North -- Room N226, Level 2, Oral
Division of Carbohydrate Chemistry |
