Stephacidin A and B: two structurally novel, selective inhibitors of the testosterone-dependent prostate LNCaP cells

J Am Chem Soc. 2002 Dec 11;124(49):14556-7. doi: 10.1021/ja028538n.

Abstract

Two novel antitumor alkaloids, Stephacidin A and B, were isolated from the solid fermentation of Aspergillus ochraceus WC76466. Both alkaloids exhibit in vitro cytotoxicity against a number of human tumor cell lines; however, stephacidin B demonstrated more potent and selective antitumor activities, especially against prostate testeosterone-dependent LNCaP cells with IC50 value of 60 nM. The structures of stephacidin A and B were established on the basis of the NMR data and X-ray crystallography. With 15 rings and 9 chiral centers, stephacidin B represents one of the most structurally complex and novel alkaloids occurring in nature.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Aspergillus ochraceus / chemistry*
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Humans
  • Indole Alkaloids
  • Indoles / chemistry*
  • Indoles / isolation & purification*
  • Indoles / pharmacology
  • Male
  • Molecular Structure
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / pathology
  • Nuclear Magnetic Resonance, Biomolecular
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Testosterone / physiology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Indole Alkaloids
  • Indoles
  • stephacidin A
  • stephacidin B
  • Testosterone