Cross-linking and sequence specific alkylation of DNA BY aziridinylquinones. 1. Quinone methides.
Mayalarp, Stephen P Hargreaves, Robert H J Butler, John O'Hare, C C Hartley, John A
Mayalarp, Stephen P
Hargreaves, Robert H J
Butler, John
O'Hare, C C
Hartley, John A
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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.
Description
Date
1996-01-19
Publisher
Collections
Keywords
Cultured Tumour Cells
Type
Article
Citation
Cross-linking and sequence specific alkylation of DNA BY aziridinylquinones. 1. Quinone methides. 1996, 39 (2):531-7 J. Med. Chem.