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dc.contributor.authorMayalarp, Stephen P
dc.contributor.authorHargreaves, Robert H J
dc.contributor.authorButler, John
dc.contributor.authorO'Hare, C C
dc.contributor.authorHartley, John A
dc.date.accessioned2010-04-07T08:23:38Z
dc.date.available2010-04-07T08:23:38Z
dc.date.issued1996-01-19
dc.identifier.citationCross-linking and sequence specific alkylation of DNA BY aziridinylquinones. 1. Quinone methides. 1996, 39 (2):531-7 J. Med. Chem.en
dc.identifier.issn0022-2623
dc.identifier.pmid8558523
dc.identifier.doi10.1021/jm950629q
dc.identifier.urihttp://hdl.handle.net/10541/95802
dc.description.abstractThe cytotoxicities and DNA cross-linking abilities of 16 1,4-benzoquinones have been investigated. All of the alkylmonoaziridinyl-1,4-benzoquinones were able to interstrand crosslink DNA after reduction and were cytotoxic in vitro. Compounds lacking an aziridine group were unable to cross-link DNA and were less cytotoxic. The methyl analogues were shown to preferentially react at TGC sequences. From comparing the structural requirements for crosslinking and the cytotoxicities, a mechanism has been proposed wherein some hydroquinones can associate and react at TGC sequences in DNA. These hydroquinones can subsequently autoxidize to form a reactive quinone methide which reacts at the opposite strand to form a cross-link.
dc.language.isoenen
dc.subjectCultured Tumour Cellsen
dc.subject.meshAlkylation
dc.subject.meshAntineoplastic Agents
dc.subject.meshComputer Simulation
dc.subject.meshCross-Linking Reagents
dc.subject.meshDNA
dc.subject.meshHumans
dc.subject.meshIndolequinones
dc.subject.meshIndoles
dc.subject.meshModels, Molecular
dc.subject.meshOxidation-Reduction
dc.subject.meshQuinones
dc.subject.meshTumor Cells, Cultured
dc.titleCross-linking and sequence specific alkylation of DNA BY aziridinylquinones. 1. Quinone methides.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Biophysical Chemistry, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalJournal of Medicinal Chemistryen
html.description.abstractThe cytotoxicities and DNA cross-linking abilities of 16 1,4-benzoquinones have been investigated. All of the alkylmonoaziridinyl-1,4-benzoquinones were able to interstrand crosslink DNA after reduction and were cytotoxic in vitro. Compounds lacking an aziridine group were unable to cross-link DNA and were less cytotoxic. The methyl analogues were shown to preferentially react at TGC sequences. From comparing the structural requirements for crosslinking and the cytotoxicities, a mechanism has been proposed wherein some hydroquinones can associate and react at TGC sequences in DNA. These hydroquinones can subsequently autoxidize to form a reactive quinone methide which reacts at the opposite strand to form a cross-link.


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