Bioorganic & Medicinal Chemistry Letters 2009-02-15

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

Ryan M Phelan, Marc Ostermeier, Craig A Townsend

Index: Bioorg. Med. Chem. Lett. 19(4) , 1261-3, (2009)

Full Text: HTML

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.


Related Compounds

Related Articles:

A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening.

2015-01-01

[Biomed Res. Int. 2015 , 419383, (2015)]

Identification of peptide inhibitors of penicillinase using a phage display library.

2016-02-01

[Anal. Biochem. 494 , 4-9, (2015)]

Outbreak of PER-1 and diversity of β-lactamases among ceftazidime-resistant Pseudomonas aeruginosa clinical isolates.

2014-03-01

[J. Med. Microbiol. 63(Pt 3) , 386-92, (2014)]

Comparative in-vitro activity of cefoperazone-tazobactam and cefoperazone-sulbactam combinations against ESBL pathogens in respiratory and urinary infections.

2012-11-01

[J. Assoc. Physicians India 60 , 22-4, (2012)]

Looking for the new preparations for antibacterial therapy. II. Clinical trials; new beta-lactam antibiotics and beta-lactamase inhibitors.

2013-01-01

[Przegl. Epidemiol. 67(1) , 51-6, 135-40, (2013)]

More Articles...