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Titolo:
Generation of hydroxyl radicals by the antiviral compound phosphonoformic acid (foscarnet)
Autore:
Lindqvist, C; Nordstrom, T;
Indirizzi:
Abo Akad Univ, Dept Biochem & Pharm, FIN-20521 Turku, Finland Abo Akad Univ Turku Finland FIN-20521 & Pharm, FIN-20521 Turku, Finland Abo Akad Univ, Dept Biol, FIN-20521 Turku, Finland Abo Akad Univ Turku Finland FIN-20521 ept Biol, FIN-20521 Turku, Finland
Titolo Testata:
PHARMACOLOGY & TOXICOLOGY
fascicolo: 1, volume: 89, anno: 2001,
pagine: 49 - 55
SICI:
0901-9928(200107)89:1<49:GOHRBT>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
HERPES-SIMPLEX VIRUS; PHARMACOKINETIC PROPERTIES; IMMUNOCOMPROMISED PATIENTS; CYTOMEGALOVIRUS RETINITIS; PYROPHOSPHATE ANALOGS; REVERSE-TRANSCRIPTASE; SUPEROXIDE-DISMUTASE; THERAPEUTIC USE; IRON; INHIBITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Nordstrom, T Abo Akad Univ, Dept Biochem & Pharm, BioCity POB 66, FIN-20521 Turku, Finland Abo Akad Univ BioCity POB 66 Turku Finland FIN-20521 Finland
Citazione:
C. Lindqvist e T. Nordstrom, "Generation of hydroxyl radicals by the antiviral compound phosphonoformic acid (foscarnet)", PHARM TOX, 89(1), 2001, pp. 49-55

Abstract

Phosphonoformic acid (foscarnet) is an antiviral agent that is used to treat severe cytomegalovirus infections in AIDS patients. We demonstrate by using the ferrous iron indicator Ferrozine and ascorbic acid (vitamin C) thatfoscarnet can chelate ferric iron and form a redox-active iron complex. Byusing the hydroxyl radical indicator coumarin-3-carboxylic acid we found that the foscarnet-Fe-3 complex formed can readily catalyze hydroxyl radical((OH)-O-.) generation by the Fenton reaction: (Fe2+ + H2O2 -->Fe3+ + (OH)-O-. + -OH) if hydrogen peroxide and ascorbic acid are present. Hydroxylation of coumarin-3-carboxylic acid could be blocked by addition of known hydroxyl radical scavengers such as mannitol, sucrose, glucose and dimethyl sulfoxide. Moreover, by using a DNA nicking assay, we found that foscarnet catalyzed hydroxyl radicals can induce single strand brakes in DNA. The potencyof the hydroxyl radicals formed to induce damage could also be demonstrated in a phosphate-free buffer where the hydroxyl radicals formed attacked and liberated phosphate from the foscarnet molecule. Our results indicate that foscarnet catalyzed hydroxyl radical formation might take place during conditions where a peroxide generating system(s), vitamin C and transitions metals are present.

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Documento generato il 22/09/20 alle ore 22:36:17