Madindoline, a novel inhibitor of IL-6 activity from Streptomyces sp. K93-0711. I. Taxonomy, fermentation, isolation and biological activities

J Antibiot (Tokyo). 1996 Nov;49(11):1091-5. doi: 10.7164/antibiotics.49.1091.

Abstract

Selective growth inhibition against IL-6-dependent cells was detected in fermentation extracts of a microbial strain, K93-0711, which was characterized as Streptomyces species. Active metabolite, termed madindoline A and B, were isolated, and the structure was determined to be 3a-hydroxy-indoline with diketocyclopentene at the N position. Madindoline A and B displayed dose-dependent inhibition of MH60 cells, an IL-6-dependent cell line, in presence of 0.1 U/ml IL-6. The IC50 for madindoline A and B against this cell line was 8 microM and 30 microM, respectively. These compounds did not inhibit the growth of cell lines which are not IL-6 dependent and the growth inhibition of the MH60 cell line was reversed by addition of excess, 0.4 U/ml, of IL-6 to the culture media. These compounds did not show any antimicrobial activity at a concentration of 1,000 micrograms/ml.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bridged Bicyclo Compounds, Heterocyclic / isolation & purification*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cell Division / drug effects
  • Cells, Cultured
  • Fermentation
  • Humans
  • Indoles / isolation & purification*
  • Indoles / pharmacology
  • Interleukin-6 / antagonists & inhibitors*
  • Leukemia, Experimental / drug therapy
  • Streptomyces

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Indoles
  • Interleukin-6
  • madindoline A