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  • Title: Levodopa and dopamine analogs: melanin precursors as antitumor agents in experimental human and murine leukemia.
    Author: Wick MM.
    Journal: Cancer Treat Rep; 1979 Jun; 63(6):991-7. PubMed ID: 466656.
    Abstract:
    L-Dopa methyl ester has been shown to be a novel antitumor agent. Furthermore, the L-dopa analogs, D-dopa, alpha-methyldopa, and dopamine, also exhibit significant antitumor activity in the L1210 and P388 lymphocytic leukemia systems. Structure-activity studies confirmed that the presence of a catechol moiety was essential for activity. Two analogs, 3,4-dihydroxybenzylamine and N-acetyldopamine, which were much less neurotoxic, exhibited the greatest antitumor activity. In vitro, at concentrations from 0.5 to 3.0 mM, there is a rapid and profound inhibition of radiolabeled thymidine incorporation as compared to uridine or leucine incorporation. Continuous exposure of exponentor up to 24 hours resulted in a block of traverse of cells through the cell cycle in G1 coupled with a depletion of cells with a G2 complement of DNA. In vivo, toxicity of these compounds appears to be mediated principally by conversion to dopamine. Similar effects upon thymidine incorporation were observed in human leukemia cells in vitro.
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