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  • Title: Synthesis and biologic evaluation of the dopamine analog N-acetyldopamine in experimental leukemia in mice.
    Author: Wick MM, Mui A.
    Journal: J Natl Cancer Inst; 1981 Feb; 66(2):351-4. PubMed ID: 6935484.
    Abstract:
    N-Acetyldopamine is a relatively nontoxic analog of dopamine that has shown significant antitumor activity in experimental L1210 and P388 leukemias. A convenient two-step chemical synthesis of this derivative provided a sufficient quantity of material to study the effects of the administration of this drug by a more frequent schedule. The antitumor activity in the L1210 and P388 systems was significantly improved when N-acetyldopamine was administered to (C57BL/6J x DBA/2)F1 (B6D2F1) mice three times daily for 4 days. Long-term survivors appeared, which indicated tumor kills in excess of 10(5) cells. The effects of dopamine and N-acetyldopamine on the incorporation of radioactively labeled thymidine (dThd) by proliferating tissues (tumor, bone marrow, and gastrointestinal mucosa) were examined in tumor-bearing B6D2F1 mice. The dThd incorporation into tumor cells was selectively inhibited in both the L1210 and P388 leukemias with less inhibition of bone marrow and gastrointestinal mucosa cells. One hour after a dose of 400 mg N-acetyldopamine/kg, dThd incorporation was completely suppressed by both P388 and L1210 tumor cells with minimal effects on bone marrow or gastrointestinal mucosa cells. The synthetic method reported here is applicable to the preparation of various derivatives for study.
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