Cross-linking and sequence specific alkylation of DNA BY aziridinylquinones. 1. Quinone methides.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95802
Title:
Cross-linking and sequence specific alkylation of DNA BY aziridinylquinones. 1. Quinone methides.
Authors:
Mayalarp, Stephen P; Hargreaves, Robert H J; Butler, John; O'Hare, C C; Hartley, John A
Abstract:
The 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.
Affiliation:
CRC Department of Biophysical Chemistry, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Cross-linking and sequence specific alkylation of DNA BY aziridinylquinones. 1. Quinone methides. 1996, 39 (2):531-7 J. Med. Chem.
Journal:
Journal of Medicinal Chemistry
Issue Date:
19-Jan-1996
URI:
http://hdl.handle.net/10541/95802
DOI:
10.1021/jm950629q
PubMed ID:
8558523
Type:
Article
Language:
en
ISSN:
0022-2623
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMayalarp, Stephen Pen
dc.contributor.authorHargreaves, Robert H Jen
dc.contributor.authorButler, Johnen
dc.contributor.authorO'Hare, C Cen
dc.contributor.authorHartley, John Aen
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.en
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

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