Selective incorporation of the prototype melanoma seeker thiourea into nascent melanin: a chemical insight.

Abstract:

:The mechanism of selective incorporation of thiourea into melanotic melanoma was investigated by model experiments in which the effect of the compound was examined at various stages of melanogenesis in vitro. Up to 50% inhibition of dopachrome formation was observed in the tyrosinase-dopa reaction in the presence of thiourea at a 2:1 molar ratio with respect to the substrate. Under these conditions, a major product was formed which was isolated and identified as a 1:1 dopa-thiourea adduct (adduct I). Subsequent stages of the oxidation were characterized by the development of a yellow chromophore (lambdamax 440-460nm), virtually identical to that obtained by separate oxidation of the adduct I. A less remarkable effect of thiourea was observed on the oxidative polymerization of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) which was apparent on spectrophotometric and high pressure liquid chromatography (HPLC) analysis. Radiolabelling experiments with 14C-thiourea showed that the label was initially incorporated into the adduct I, while in the subsequent stages of the oxidation it was associated with pigmented materials which escaped direct analysis. Incorporation of labelled thiourea into dopa-melanins was found to be significantly higher than incorporation into synthetic pigments from indole precursors. These results provide a chemical basis for the interpretation of the selective accumulation of thiourea in those melanoma areas with high rates of melanin synthesis seen in autoradiographic experiments.

journal_name

Melanoma Res

journal_title

Melanoma research

authors

Palumbo A,Mårs U,De Martino L,d'Ischia M,Napolitano A,Larsson BS,Prota G

doi

10.1097/00008390-199712000-00006

subject

Has Abstract

pub_date

1997-12-01 00:00:00

pages

478-85

issue

6

eissn

0960-8931

issn

1473-5636

journal_volume

7

pub_type

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