Abstract
An efficient synthesis of a 5-fluorouracil-cephalosporin prodrug is described for use against colorectal and other cancers in antibody and gene-directed therapies. The compound shows stability in aqueous media until specifically activated by beta-lactamase (betaL). The kinetic parameters of the 5-fluorouracil-cephalosporin conjugate were determined in the presence of Enterobacter cloacae P99 betaL (ECl betaL) revealing a K(m)=95.4 microM and V(max)=3.21 microMol min(-1) mg(-1). The data compare favorably to related systems that have been reported and enable testing of this prodrug against cancer cell lines in vitro and in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents* / chemical synthesis
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Antineoplastic Agents* / chemistry
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Antineoplastic Agents* / pharmacology
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Cephalosporins / chemical synthesis
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Cephalosporins / metabolism
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Drug Screening Assays, Antitumor
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Enterobacter cloacae / enzymology*
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Fluorouracil* / analogs & derivatives
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Fluorouracil* / chemical synthesis
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Fluorouracil* / pharmacology
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / pharmacology*
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beta-Lactamases / immunology
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beta-Lactamases / metabolism*
Substances
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Antineoplastic Agents
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Cephalosporins
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Prodrugs
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beta-Lactamases
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Fluorouracil