Cross-linking and sequence-specific alkylation of DNA by aziridinylquinones. 3. Effects of alkyl substituents.

2.50
Hdl Handle:
http://hdl.handle.net/10541/91340
Title:
Cross-linking and sequence-specific alkylation of DNA by aziridinylquinones. 3. Effects of alkyl substituents.
Authors:
Hargreaves, Robert H J; O'Hare, C Caroline; Hartley, John A; Ross, David; Butler, John
Abstract:
The cytotoxicities and DNA cross-linking abilities of several alkyl-substituted diaziridinylquinones have been investigated. The cytotoxicities were determined in DT-diaphorase-rich (H460 and HT29) and -deficient (H596 and BE) cell lines. It was shown that the cytotoxicities in these cell lines correlated with the relative rates of reduction by the purified human enzyme and with the cross-linking efficiencies. The rates of reduction by DT-diaphorase were more dependent on the structures of the compounds than the reduction potentials, as determined by cyclic voltammetry. A computer model was also used to explain high efficiency of cross-linking and the GNC sequence selectivity of the reduced methyl-substituted diaziridinylquinones.
Affiliation:
CRC Section of Drug Development and Imaging, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 9BX, U. K.
Citation:
Cross-linking and sequence-specific alkylation of DNA by aziridinylquinones. 3. Effects of alkyl substituents. 1999, 42 (12):2245-50 J. Med. Chem.
Journal:
Journal of Medicinal Chemistry
Issue Date:
17-Jun-1999
URI:
http://hdl.handle.net/10541/91340
DOI:
10.1021/jm991007y
PubMed ID:
10377230
Type:
Article
Language:
en
ISSN:
0022-2623
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHargreaves, Robert H Jen
dc.contributor.authorO'Hare, C Carolineen
dc.contributor.authorHartley, John Aen
dc.contributor.authorRoss, Daviden
dc.contributor.authorButler, Johnen
dc.date.accessioned2010-02-08T11:05:38Z-
dc.date.available2010-02-08T11:05:38Z-
dc.date.issued1999-06-17-
dc.identifier.citationCross-linking and sequence-specific alkylation of DNA by aziridinylquinones. 3. Effects of alkyl substituents. 1999, 42 (12):2245-50 J. Med. Chem.en
dc.identifier.issn0022-2623-
dc.identifier.pmid10377230-
dc.identifier.doi10.1021/jm991007y-
dc.identifier.urihttp://hdl.handle.net/10541/91340-
dc.description.abstractThe cytotoxicities and DNA cross-linking abilities of several alkyl-substituted diaziridinylquinones have been investigated. The cytotoxicities were determined in DT-diaphorase-rich (H460 and HT29) and -deficient (H596 and BE) cell lines. It was shown that the cytotoxicities in these cell lines correlated with the relative rates of reduction by the purified human enzyme and with the cross-linking efficiencies. The rates of reduction by DT-diaphorase were more dependent on the structures of the compounds than the reduction potentials, as determined by cyclic voltammetry. A computer model was also used to explain high efficiency of cross-linking and the GNC sequence selectivity of the reduced methyl-substituted diaziridinylquinones.en
dc.language.isoenen
dc.subject.meshAntineoplastic Agents, Alkylating-
dc.subject.meshAziridines-
dc.subject.meshCell Line-
dc.subject.meshCross-Linking Reagents-
dc.subject.meshDNA-
dc.subject.meshHumans-
dc.subject.meshModels, Molecular-
dc.subject.meshNAD(P)H Dehydrogenase (Quinone)-
dc.subject.meshQuinones-
dc.titleCross-linking and sequence-specific alkylation of DNA by aziridinylquinones. 3. Effects of alkyl substituents.en
dc.typeArticleen
dc.contributor.departmentCRC Section of Drug Development and Imaging, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 9BX, U. K.en
dc.identifier.journalJournal of Medicinal Chemistryen

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