Oxidation of carbidopa by tyrosinase and its effect on murine melanoma.
Oxidation of the anti-Parkinsonian agent carbidopa by tyrosinase was investigated. The products of this reaction were identified as 3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid and 6,7-dihydroxy-3-methylcinnoline. These results demonstrate that after oxidation of the catechol moiety to an o-quinone either a redox exchange with the hydrazine group or a cyclization reaction occur. The cyclization product underwent additional oxidation reactions leading to aromatization. The cyclization reaction is undesired in the case of hydrazine-containing anti-melanoma prodrugs and will have to be taken into account in designing such compounds. Carbidopa was tested against B16(F10) melanoma cells in culture and showed cytotoxicity significantly higher than either of its oxidation products and l-dopa. This effect, however, was not specific to this cell line.
Gasowska-Bajger
Beata
B
Faculty of Chemistry, University of Opole, Ul. Oleska 48, 45-052 Opole, Poland.
Frackowiak-Wojtasek
Bozena
B
Koj
Sabina
S
Cichoń
Tomasz
T
Smolarczyk
Ryszard
R
Szala
Stanisław
S
Wojtasek
Hubert
H
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D002230:Carbidopa / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D045744:Cell Line, Tumor; D003500:Cyclization; D004295:Dihydroxyphenylalanine / Q000633:toxicity; D008545:Melanoma / Q000201:enzymology*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010084:Oxidation-Reduction; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity
D000970:Antineoplastic Agents; D011355:Prodrugs; D004295:Dihydroxyphenylalanine; D014442:Monophenol Monooxygenase; D002230:Carbidopa