Cross-linking and sequence specific alkylation of DNA BY aziridinylquinones. 1. Quinone methides.
AffiliationCRC Department of Biophysical Chemistry, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
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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.
CitationCross-linking and sequence specific alkylation of DNA BY aziridinylquinones. 1. Quinone methides. 1996, 39 (2):531-7 J. Med. Chem.
JournalJournal of Medicinal Chemistry