alexa Cell cycle arrest and antitumor activity of pironetin and its derivatives.
Chemistry

Chemistry

Medicinal Chemistry

Author(s): Kondoh M, Usui T, Kobayashi S, Tsuchiya K, Nishikawa K,

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Abstract The biological effects of pironetin and its derivatives on cell cycle progression and antitumor activity were studied. At 10-20 ng/ml, both pironetin and its demethyl derivative, NK10958P completely inhibited the cell proliferation of 3Y1 cells, however, epoxypironetin showed only a weak inhibitory activity. The cell cycle analysis revealed that these compounds arrested the cell cycle progression at the M-phase in a dose-dependent manner. These antiproliferative effects of pironetin were also observed in the range 5-25 ng/ml with several tumor cell lines. In CDF1-SLC mice bearing P388 leukemia cells, the intraperitoneal administration of 6.3 mg/kg pironetin over a 5-day period showed a moderate antitumor effect (T/C, 128\%). As the chemical structure of pironetin is different from other M-phase inhibitors such as colchicine or vinblastine, pironetin will be the lead compound for a potential new antitumor drug.
This article was published in Cancer Lett and referenced in Medicinal Chemistry

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