TY - JOUR
T1 - Identification of 2,3-diaminophenazine and of o-benzoquinone dioxime as the major in vitro metabolites of benzofuroxan
AU - Grosa, G.
AU - Galli, U.
AU - Rolando, B.
AU - Fruttero, R.
AU - Gervasio, G.
AU - Gasco, A.
N1 - Funding Information:
Work was supported by a MIUR grant (COFIN 2001). The authors gratefully thank Professor Bernard Testa for useful advice and valuable discussions.
PY - 2004/4
Y1 - 2004/4
N2 - 1. The results of an in vitro study of the metabolism of benzofuroxan using either cytosolic or microsomal fractions obtained from rat liver are reported. 2. Benzofuroxan was incubated with an appropriate volume of cytosol or microsomal suspension; control incubations were performed without the β-nicotinamide adenine dinucleotide phosphate-generating system or, alternatively, by using the subcellular fractions inactivated by heating. Incubation mixtures were analysed by high-performance liquid chromatography. Two principal metabolites (M1, M2) were identified in the cytosolic fraction only. The dependence of M2 formation on thiol cofactors, incubation time and protein concentration was examined. 3. The two metabolites were isolated and characterized by their 1H-, 13C-nuclear magnetic resonance, infrared and mass spectra. The structures of o-benzoquinonedioxime (2) and 2,3-diaminopleuozuc (3), were arranged to M1 and M2 respectively. The proposed structures were confirmed by the identity of the metabolites with authentic samples obtained by synthesis. X-ray analysis showed that the dioxime metabolite had an amphy configuration. 4. A metabolic scheme for the formation of the two products is proposed.
AB - 1. The results of an in vitro study of the metabolism of benzofuroxan using either cytosolic or microsomal fractions obtained from rat liver are reported. 2. Benzofuroxan was incubated with an appropriate volume of cytosol or microsomal suspension; control incubations were performed without the β-nicotinamide adenine dinucleotide phosphate-generating system or, alternatively, by using the subcellular fractions inactivated by heating. Incubation mixtures were analysed by high-performance liquid chromatography. Two principal metabolites (M1, M2) were identified in the cytosolic fraction only. The dependence of M2 formation on thiol cofactors, incubation time and protein concentration was examined. 3. The two metabolites were isolated and characterized by their 1H-, 13C-nuclear magnetic resonance, infrared and mass spectra. The structures of o-benzoquinonedioxime (2) and 2,3-diaminopleuozuc (3), were arranged to M1 and M2 respectively. The proposed structures were confirmed by the identity of the metabolites with authentic samples obtained by synthesis. X-ray analysis showed that the dioxime metabolite had an amphy configuration. 4. A metabolic scheme for the formation of the two products is proposed.
UR - https://www.scopus.com/pages/publications/2442565699
U2 - 10.1080/0049825042000203975
DO - 10.1080/0049825042000203975
M3 - Article
SN - 0049-8254
VL - 34
SP - 345
EP - 352
JO - Xenobiotica
JF - Xenobiotica
IS - 4
ER -