Cross-linking and sequence specific alkylation of DNA BY aziridinylquinones. 1. Quinone methides.
Affiliation
CRC Department of Biophysical Chemistry, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.Issue Date
1996-01-19
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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.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 ChemistryDOI
10.1021/jm950629qPubMed ID
8558523Type
ArticleLanguage
enISSN
0022-2623ae974a485f413a2113503eed53cd6c53
10.1021/jm950629q
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