Cross-linking and sequence specific alkylation of DNA BY aziridinylquinones. 1. Quinone methides.
Basic Information
ID: ALA1129666
Journal: J Med Chem
Title: Cross-linking and sequence specific alkylation of DNA BY aziridinylquinones. 1. Quinone methides.
Authors: Mayalarp SP, Hargreaves RH, Butler J, O'Hare CC, Hartley JA.
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.
CiteXplore: 8558523
DOI: 10.1021/jm950629q
Patent ID: ┄