Pironetin

Structure
NPEdia (re-discovered compound)
Pironetin
Producing organism
Streptomyces sp.
Biological activity
tubulin disassembler
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.
References
isolation and structural determination
  • Kobayashi S, Tsuchiya K, Harada T, Nishide M, Kurokawa T, Nakagawa T, Shimada N, Kobayashi K.: Pironetin, a novel plant growth regulator produced by Streptomyces sp. NK10958. I. Taxonomy, production, isolation and preliminary characterization.
    J Antibiot, 47(6): 697-702 (1994) PMID: 8040075
  • Kobayashi S, Tsuchiya K, Kurokawa T, Nakagawa T, Shimada N, Iitaka Y.: Pironetin, a novel plant growth regulator produced by Streptomyces sp. NK10958. II. Structural elucidation.
    J Antibiot, 47(6): 703-707 (1994) PMID: 7794417
  • Kobayashi S, Tsuchiya K, Nishide M, Nishikiori T, Nakagawa T, Shimada N.: Pironetin, a novel plant growth regulator produced by Streptomyces sp. NK10958. III. Biosynthesis.
    J Antibiot, 48(8): 893-895 (1995) PMID: 7592038
  • biological activity as new roles
  • Kondoh M, Usui T, Kobayashi S, Tsuchiya K, Nishikawa K, Nishikiori T, Mayumi T, Osada H.: Cell cycle arrest and antitumor activity of pironetin and its derivatives.
    Cancer Lett, 126(1): 29-32 (1998) PMID: 9563645
  • Kondoh M, Usui T, Nishikiori T, Mayumi T, Osada H.: Apoptosis induction via microtubule disassembly by an antitumour compound, pironetin.
    Biochem J, 340( Pt 2): 411-416 (1999) PMID: 10333483
  • Simizu S, Shibasaki F, Osada H.: Bcl-2 inhibits calcineurin-mediated Fas ligand expression in antitumor drug-treated baby hamster kidney cells.
    Jpn J Cancer Res, 91(7): 706-714 (2000) PMID: 10920278
  • structure-activity relationship
  • Watanabe H, Watanabe H, Usui T, Kondoh M, Osada H, Kitahara T.: Synthesis of pironetin and related analogs: studies on structure-activity relationships as tubulin assembly inhibitors.
    J Antibiot, 53(5): 540-545 (2000) PMID: 10908119
  • Additional information