Cp. Saris et al., CHEMICAL-PROPERTIES OF THE ULTIMATE METABOLITES OF 2-AMINO-5-PHENYLPYRIDINE (PHE-P-1) AND ITS ORTHO-METHYL DERIVATIVE, Chemico-biological interactions, 95(1-2), 1995, pp. 29-40
The reactivity of the N-acetoxy metabolite of 2-amino-5-phenylpyridine
(Phe-P-l), a pyrolysis product of phenylalanine, towards 2'-deoxyguan
osine (dG), 2'-deoxyguanosine-3'-monophosphate (dGMP) and DNA was stud
ied and compared with that of the ortho-methyl derivative. Reaction of
2-acetoxyamino-5-phenylpyridine (N-OAc-APP) with dG resulted in subst
itution at the 8-position of this nucleoside by the ortho carbon of th
e amine. The major reaction, however, was acetylation of dG. Iii contr
ast, 2-acetoxyamino-3-methyl-5-phenylpyridine (N-OAc-MeAPP) mainly att
acked the 8-position of dG by the exocyclic nitrogen and hardly any ac
etylation of the nucleoside occurred. The adducts were chromatographic
ally isolated and characterized by their mass and NMR spectra. Upon re
action of N-acetoxy compounds with DNA and dGMP, formation of the same
adducts was observed, besides the formation of minor amounts of unide
ntified compounds, as was established by P-32-postlabeIIing analysis.
The amount of DNA-bound amine, formed by the interaction of N-OAc-APP
with DNA, was similar to 15 times smaller than that observed after the
reaction with the corresponding ortho-methyl derivative under the sam
e conditions.