Mitoguazone is a guanylhydrazone with potential antineoplastic activity. Mitoguazone competitively inhibits S-adenosyl-L-methionine decarboxylase (SAMD), an enzyme involved in the synthesis of polyamines, resulting in decreased proliferation of tumor cells, antimitochondrial effects, and p53-independent apoptosis. Polyamines, specifically spermine and spermidine, are essential for thymidine kinase production, DNA synthesis, and cell proliferation.
Mitoguazone, also known as Methylglyoxal-bis(guanylhydrazone), is a synthetic polycarbony derivative with potent antitumour activity. Mitoguazone is a brain-permeable, competitive inhibitor of SAMDC, which disrupts polyamine biosynthesis. Mitoguazone induces apoptosis. Mitoguazone inhibits the integration of HIV DNA into the cellular DNA of monocytes and macrophages. Mitoguazone has therapeutic potential for acute leukaemia, Hodgkin's lymphoma and non-Hodgkin's lymphoma[1][2][3][4].At concentrations as low as 0.5 μg/mL, Mitoguazone competitively inhibits spermine synthesis in lymphocytes. At concentrations of 30 μg/mL or higher, Mitoguazone inhibits protein synthesis and mitochondrial respiration[1].Mitoguazone induces apoptosis in Burkitt's lymphoma cell lines (Raji, Ramos and Daudi) and prostate carcinoma cell line (MPC 3), with apoptosis correlating with concentration and time, and induces p53-independent programmed cell death in human breast cancer MCF7 cell line[2].
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