2.50
Hdl Handle:
http://hdl.handle.net/10541/109024
Title:
Redox cycling of potential antitumor aziridinyl quinones.
Authors:
Lusthof, K J; De Mol, N J; Richter, W; Janssen, L H; Butler, John; Hoey, Brigid M; Verboom, Willem; Reinhoudt, David N
Abstract:
The formation of reactive oxygen intermediates (ROI) during redox cycling of newly synthesized potential antitumor 2,5-bis (1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives has been studied by assaying the production of ROI (superoxide, hydroxyl radical, and hydrogen peroxide) by xanthine oxidase in the presence of BABQ derivatives. At low concentrations (< 10 microM) some BABQ derivatives turned out to inhibit the production of superoxide and hydroxyl radicals by xanthine oxidase, while the effect on the xanthine-oxidase-induced production of hydrogen peroxide was much less pronounced. Induction of DNA strand breaks by reactive oxygen species generated by xanthine oxidase was also inhibited by BABQ derivatives. The DNA damage was comparable to the amount of hydroxyl radicals produced. The inhibiting effect on hydroxyl radical production can be explained as a consequence of the lowered level of superoxide, which disrupts the Haber-Weiss reaction sequence. The inhibitory effect of BABQ derivatives on superoxide formation correlated with their one-electron reduction potentials: BABQ derivatives with a high reduction potential scavenge superoxide anion radicals produced by xanthine oxidase, leading to reduced BABQ species and production of hydrogen peroxide from reoxidation of reduced BABQ. This study, using a unique series of BABQ derivatives with an extended range of reduction potentials, demonstrates that the formation of superoxide and hydroxyl radicals by bioreductively activated antitumor quinones can in principle be uncoupled from alkylating activity.
Affiliation:
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Utrecht University, Sorbonnelaan, The Netherlands.
Citation:
Redox cycling of potential antitumor aziridinyl quinones. 1992, 13 (6):599-608 Free Radic. Biol. Med.
Journal:
Free Radical Biology & Medicine
Issue Date:
Dec-1992
URI:
http://hdl.handle.net/10541/109024
DOI:
10.1016/0891-5849(92)90034-E
PubMed ID:
1334033
Type:
Article
Language:
en
ISSN:
0891-5849
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLusthof, K Jen
dc.contributor.authorDe Mol, N Jen
dc.contributor.authorRichter, Wen
dc.contributor.authorJanssen, L Hen
dc.contributor.authorButler, Johnen
dc.contributor.authorHoey, Brigid Men
dc.contributor.authorVerboom, Willemen
dc.contributor.authorReinhoudt, David Nen
dc.date.accessioned2010-08-04T09:28:04Z-
dc.date.available2010-08-04T09:28:04Z-
dc.date.issued1992-12-
dc.identifier.citationRedox cycling of potential antitumor aziridinyl quinones. 1992, 13 (6):599-608 Free Radic. Biol. Med.en
dc.identifier.issn0891-5849-
dc.identifier.pmid1334033-
dc.identifier.doi10.1016/0891-5849(92)90034-E-
dc.identifier.urihttp://hdl.handle.net/10541/109024-
dc.description.abstractThe formation of reactive oxygen intermediates (ROI) during redox cycling of newly synthesized potential antitumor 2,5-bis (1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives has been studied by assaying the production of ROI (superoxide, hydroxyl radical, and hydrogen peroxide) by xanthine oxidase in the presence of BABQ derivatives. At low concentrations (< 10 microM) some BABQ derivatives turned out to inhibit the production of superoxide and hydroxyl radicals by xanthine oxidase, while the effect on the xanthine-oxidase-induced production of hydrogen peroxide was much less pronounced. Induction of DNA strand breaks by reactive oxygen species generated by xanthine oxidase was also inhibited by BABQ derivatives. The DNA damage was comparable to the amount of hydroxyl radicals produced. The inhibiting effect on hydroxyl radical production can be explained as a consequence of the lowered level of superoxide, which disrupts the Haber-Weiss reaction sequence. The inhibitory effect of BABQ derivatives on superoxide formation correlated with their one-electron reduction potentials: BABQ derivatives with a high reduction potential scavenge superoxide anion radicals produced by xanthine oxidase, leading to reduced BABQ species and production of hydrogen peroxide from reoxidation of reduced BABQ. This study, using a unique series of BABQ derivatives with an extended range of reduction potentials, demonstrates that the formation of superoxide and hydroxyl radicals by bioreductively activated antitumor quinones can in principle be uncoupled from alkylating activity.en
dc.language.isoenen
dc.subject.meshAntineoplastic Agents-
dc.subject.meshAziridines-
dc.subject.meshDNA Damage-
dc.subject.meshFree Radicals-
dc.subject.meshHydrogen Peroxide-
dc.subject.meshHydroxides-
dc.subject.meshHydroxyl Radical-
dc.subject.meshOxidation-Reduction-
dc.subject.meshQuinones-
dc.subject.meshReactive Oxygen Species-
dc.subject.meshSuperoxides-
dc.subject.meshXanthine Oxidase-
dc.titleRedox cycling of potential antitumor aziridinyl quinones.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Utrecht University, Sorbonnelaan, The Netherlands.en
dc.identifier.journalFree Radical Biology & Medicineen
All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.