The influence of side-chain structure on the mode of reaction of ortho-quinone amines has been investigated with a view, ultimately, to developing potential methods of therapeutic intervention by manipulating the early stages of melanogenesis. Four N-substituted dopamine derivatives have been prepared and quinone formation studied using pulse radiolysis and tyrosinase-oximetry. Ortho-quinones with an amide or urea side chain were relatively stable, although evidence for slow formation of isomeric para-quinomethanes was observed. A thiourea derivative cyclized fairly rapidly (k = 1.7/s) to a product containing a seven-membered ring, whereas a related amidine gave more rapidly (k approximately 2.5 x 10(2)/s) a stable spirocyclic product. The results suggest that cyclization of amides, ureas and carbamates (NHCO-X; X = R, NHR or OR) does not occur and is not, therefore, a viable approach to the formation of tyrosinase-activated antimelanoma prodrugs. It is also concluded that for N-acetyldopamine spontaneous ortho-quinone to para-quinomethane isomerization is slow.
- MeSH
- Agaricus enzymologie MeSH
- antitumorózní látky chemie terapeutické užití MeSH
- dopamin analogy a deriváty chemie MeSH
- financování organizované MeSH
- fungální proteiny chemie MeSH
- isomerie MeSH
- melaniny chemická syntéza chemie MeSH
- melanom enzymologie farmakoterapie MeSH
- molekulární struktura MeSH
- nádorové proteiny chemie MeSH
- oxidace-redukce MeSH
- prekurzory léčiv chemie MeSH
- tyrosinasa chemie MeSH
