Peroxidation of the antimalarial drug primaquine: characterization of a benzidine-like metabolite with methaemoglobin-forming activity.
1. An organic solvent-extractable product was obtained from incubations of primaquine (70 mM) with H2O2 (70mM) and horseradish peroxidase (0.5 mg/ml) in acetate buffer, pH4.2. 2. The metabolite was characterized as 5,5-di-(8-[(4-amino-1-methylbutyl)amino]-6-methoxyquinoline) by 1H-n.m.r., mass, FT-i.r. and u.v.-visible spectroscopy. 3. Incubations of rat erythrocytes with 5,5-di-(8-[(4-amino-1-methylbutyl)amino]-6-methoxyquinoline) led to the formation of methaemoglobin in a time- and metabolite concentration-dependent manner.
Department of Biochemistry, Universidade de São Paulo, Brazil.
M da S
Mda S
Morais
O
O
Augusto
D000634:Aminoquinolines / Q000737:chemistry*; D000818:Animals; D001560:Benzidines / Q000378:metabolism / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000378:metabolism; D008297:Male; D008706:Methemoglobin / Q000096:biosynthesis*; D008708:Methemoglobinemia / Q000139:chemically induced; D010084:Oxidation-Reduction; D011319:Primaquine / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000634:Aminoquinolines; D001560:Benzidines; D006454:Hemoglobins; D008706:Methemoglobin; D006735:Horseradish Peroxidase; D011319:Primaquine