Novel selective inhibitors for human topoisomerase I, BM2419-1 and -2 derived from saintopin

J Antibiot (Tokyo). 1998 Dec;51(12):1069-74. doi: 10.7164/antibiotics.51.1069.

Abstract

Compounds BM2419-1 and -2 were isolated from a culture broth of a fungus Paecilomyces sp. BM2419. It was shown that these novel compounds were artifacts derived from saintopin, a dual inhibitor of topoisomerase I and II by independent processes. In the human topoisomerase I inhibition assay using the recombinant Saccharomyces cerevisiae, BM2419-1 and -2 inhibited selectively the yeast growth dependent on human topoisomerase I induction with IC50 values of 0.3 ng/ml and 6.0 ng/ml, respectively.

MeSH terms

  • Animals
  • Anthracyclines*
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / isolation & purification
  • Antibiotics, Antineoplastic / pharmacology*
  • Benz(a)Anthracenes / chemistry
  • Benz(a)Anthracenes / isolation & purification
  • Benz(a)Anthracenes / pharmacology
  • Camptothecin / pharmacology
  • Chemical Phenomena
  • Chemistry, Physical
  • DNA Topoisomerases, Type I / genetics
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Paecilomyces / chemistry
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / genetics
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Topoisomerase I Inhibitors*
  • Tumor Cells, Cultured

Substances

  • Anthracyclines
  • Antibiotics, Antineoplastic
  • BM 2419-1
  • BM 2419-2
  • Benz(a)Anthracenes
  • Enzyme Inhibitors
  • Recombinant Proteins
  • Topoisomerase I Inhibitors
  • saintopin
  • DNA Topoisomerases, Type I
  • Camptothecin