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  • Design and synthesis of a beta-lactamase activated 5-fluorouracil prodrug.

Design and synthesis of a beta-lactamase activated 5-fluorouracil prodrug.

Bioorganic & medicinal chemistry letters (2009-01-27)
Ryan M Phelan, Marc Ostermeier, Craig A Townsend
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
β-Lactamase from Enterobacter cloacae, Type IV, lyophilized powder, 0.2-0.6 units/mg protein (using benzylpenicillin)
Sigma-Aldrich
2-Thiopheneacetyl chloride, 98%