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

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

Research Abstract Table of Contents

Jump to the:

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

Ivan Spasojevi?,O Michael Colvin,Keith R Warshany,Ines Batini?-Haberle,

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.

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

I Spasojevi?,OM Colvin,KR Warshany,I Batini?-Haberle,

For similar pharmaceutical preparations: prodrugs research abstracts see: pharmaceutical preparations: prodrugs research

PUBMED ID PMID:

MEDLINE DATE:

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

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of inorganic biochemistry

VOLUME: 100

Page Numbers: 1897-902

Journal Abbreviation: J. Inorg. Biochem.

ISSN: 0162-0134

DAY: 5

MONTH: 08

YEAR: 2006

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 7905788

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

KEYWORDS: Prodrugs

MESH TERMS: metabolism

Chemical & Substance for Abstract: New approach to the activation of anti-cancer pro-drugs by metalloporphyrin-based cytochrome P450 mimics in all-aqueous biologically relevant system. Information

Substance Name: Cytochrome P-450 Enzyme System

Registry Number: 9035-51-2

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

AFFILIATION: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. spaso001@mc.duke.edu <spaso001@mc.duke.edu>

Country: United States

AGENCY: United States NCI

GRANT: CA16783

ACRONYM: CA

MEDLINETA: J Inorg Biochem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

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

• Impact of electrostatics in redox modulation of oxidative stress by Mn porphyrins: Protection of SOD-deficient Escherichia coli via alternative mechanism where Mn porphyrin acts as a Mn carrier.
• Mn porphyrin-based superoxide dismutase (SOD) mimic, MnIIITE-2-PyP5+, targets mouse heart mitochondria.
• New approach to the activation of anti-cancer pro-drugs by metalloporphyrin-based cytochrome P450 mimics in all-aqueous biologically relevant system.
• Pharmacokinetics of the potent redox-modulating manganese porphyrin, MnTE-2-PyP(5+), in plasma and major organs of B6C3F1 mice.
• Pure manganese(III) 5,10,15,20-tetrakis(4-benzoic acid)porphyrin (MnTBAP) is not a superoxide dismutase mimic in aqueous systems: a case of structure-activity relationship as a watchdog mechanism in experimental therapeutics and biology.
• Redox modulation of oxidative stress by Mn porphyrin-based therapeutics: The effect of charge distribution.
• SOD-like activity of Mn(II) beta-octabromo-meso-tetrakis(N-methylpyridinium-3-yl)porphyrin equals that of the enzyme itself.