Ultrafast Reaction of the Drug Hydralazine with Apurinic/Apyrimidinic Sites in DNA Gives Rise to a Stable Triazolo[3,4-a]phthalazine Adduct
Tanhaul Islam,
Garam Shim,
Douglas Melton
et al.
Abstract:The clinically used antihypertensive agent hydralazine
rapidly
generates hydrazone-derived adducts by reaction with apurinic/apyrimidinic
(also known as abasic or AP) sites in many different sequences of
duplex DNA. The reaction rates are comparable to those of some AP-trapping
reagents previously described as “ultrafast.” Initially,
reversible formation of a hydrazone adduct is followed by an oxidative
cyclization reaction that generates a chemically stable triazolo[3,4-a]phthalazine adduct. The net result is… Show more
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