New approach to the activation of anti-cancer pro-drugs by metalloporphyrin-based cytochrome P450 mimics in all-aqueous biologically relevant system.

Journal Article (Journal Article)

The low-molecular weight water-soluble Fe(III) and Mn(III) porphyrins--in biologically relevant phosphate-buffered saline medium with ascorbic acid as a source of electrons, under aerobic conditions but without co-oxidant - catalyze the hydroxylation of anti-cancer drug cyclophosphamide to active metabolite 4-hydroxycyclophosphamide in yields similar or higher than those typically obtained by the action of liver enzymes in vivo. The Fe(III) meso tetrakis(2,6-difluoro-3-sulfonatophenyl)porphyrin, highly electron-deficient at the metal site, was the most effective catalyst. If proven viable in vivo, this methodology could be expanded to localized or systemic activation of the entire family of oxazaphosphorine-based (and many other) anti-cancer drugs and become a powerful tool for an aggressive treatment of tumors with less toxic side effects to the patient.

Full Text

Duke Authors

Cited Authors

  • Spasojević, I; Colvin, OM; Warshany, KR; Batinić-Haberle, I

Published Date

  • November 2006

Published In

Volume / Issue

  • 100 / 11

Start / End Page

  • 1897 - 1902

PubMed ID

  • 16965820

International Standard Serial Number (ISSN)

  • 0162-0134

Digital Object Identifier (DOI)

  • 10.1016/j.jinorgbio.2006.07.013


  • eng

Conference Location

  • United States