6533b830fe1ef96bd1297c0f
RESEARCH PRODUCT
Oxidation of carbidopa by tyrosinase and its effect on murine melanoma
Stanisław SzalaHubert WojtasekBeata Gąsowska-bajgerBozena Frackowiak-wojtasekTomasz CichońRyszard SmolarczykSabina Kojsubject
TyrosinaseClinical BiochemistryPharmaceutical ScienceAntineoplastic AgentstyrosinaseBiochemistryRedoxMicechemistry.chemical_compoundCell Line TumorDrug DiscoverymedicinemelanomaAnimalsMoietyOrganic chemistryProdrugscarbidopaCytotoxicityMolecular BiologyCatecholMonophenol MonooxygenaseChemistryOrganic ChemistryAromatizationhydrazineProdrugCombinatorial chemistryDihydroxyphenylalanineCyclizationCarbidopaMolecular MedicineprodrugOxidation-Reductionmedicine.drugdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2009-07-01 | Bioorganic & Medicinal Chemistry Letters : a tetrahedron publication for the rapid dissemination of preliminary communication and all aspects of bioorganic chemistry, medicinal chemistry and related disciplines |