dc.contributor.author |
Shinde, Sujata |
en |
dc.contributor.author |
Hay, Michael |
en |
dc.contributor.author |
Patterson, Adam |
en |
dc.contributor.author |
Denny, William |
en |
dc.contributor.author |
Anderson, Robert |
en |
dc.date.accessioned |
2011-11-17T17:25:31Z |
en |
dc.date.accessioned |
2014-02-06T23:58:38Z |
en |
dc.date.issued |
2009-10-14 |
en |
dc.identifier.citation |
Journal of the American Chemical Society 131(40):14220-14221 |
en |
dc.identifier.issn |
0002-7863 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/21570 |
en |
dc.description.abstract |
The radical species produced following one-electron reduction of tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide, TPZ) by cytochrome P-450 reductase-enriched microsomes have been investigated using electron paramagnetic resonance (EPR) spectroscopy. Spin trapping with 5,5'-dimethylpyrroline 1-N-oxide (DMPO) gave a composite spectrum of a carbon-centered radical and the well-known DMPO-OH adduct. Using O-17-tabeted water resulted in a change in the EPR spectrum to that of DMPO-(OH)-O-17, indicating that this radical species is formed with solvent involvement and not from release of a (OH)-O-center dot radical from one-electron-reduced TPZ. Furthermore, using the closely related spin trap 5-diethoxyphosphoryl-5-methylpyrroline N-oxide (DEPMPO), which is less prone to oxidation than DMPO, gave only a carbon-centered radical spectrum without any involvement of a (OH)-O-center dot radical. Reduction of a more soluble analogue of TPZ, in redox: equilibrium with its 1-oxide derivative, led to spin trapping of both a carbon-centered radical and a nitrogen centered radical by N-tert-butyl-alpha-phenylnitrone (PBN). The multicentered nature of this nitrogen-centered radical spectrum provides support for the formation of a benzotriazinyl radical following one-electron reduction of this class of bioreductive drug. |
en |
dc.language |
EN |
en |
dc.publisher |
American Chemical Society |
en |
dc.relation.ispartofseries |
Journal of the American Chemical Society |
en |
dc.relation.replaces |
http://hdl.handle.net/2292/9263 |
en |
dc.relation.replaces |
2292/9263 |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0002-7863/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
3-AMINO-1,2,4-BENZOTRIAZINE 1,4-DIOXIDE |
en |
dc.subject |
ANTITUMOR AGENTS |
en |
dc.subject |
CYTOTOXICITY |
en |
dc.subject |
HYPOXIA |
en |
dc.subject |
DAMAGE |
en |
dc.subject |
METABOLISM |
en |
dc.subject |
SR-4233 |
en |
dc.subject |
CANCER |
en |
dc.subject |
POTENTIATION |
en |
dc.subject |
ACTIVATION |
en |
dc.title |
Spin Trapping of Radicals Other Than the (OH)-O-center dot Radical upon Reduction of the Anticancer Agent Tirapazamine by Cytochrome P-450 Reductase |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1021/ja906860a |
en |
pubs.issue |
40 |
en |
pubs.begin-page |
14220 |
en |
pubs.volume |
131 |
en |
dc.identifier.pmid |
19772319 |
en |
pubs.end-page |
14221 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
89023 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Auckland Cancer Research |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2010-12-09 |
en |
pubs.dimensions-id |
19772319 |
en |