Novel mammalian cell cycle inhibitors, tryprostatins A, B and other diketopiperazines produced by Aspergillus fumigatus. I. Taxonomy, fermentation, isolation and biological properties

J Antibiot (Tokyo). 1996 Jun;49(6):527-33. doi: 10.7164/antibiotics.49.527.

Abstract

Two novel diketopiperazines named tryprostatins A (1) and B (2) and a new natural product belonging to the diketopiperazine series, designated as demethoxyfumitremorgin C (3), together with four known diketopiperazines, fumitremorgin C (4), 12,13-dihydroxyfumitremorgin C (5), fumitremorgin B (6) and verruculogen (7), were isolated from the fermentation broth of Aspergillus fumigatus BM939 by the combined use of solvent extraction, silica gel column chromatography, preparative TLC and repeated-preparative HPLC. The diketopiperazines showed an inhibitory activity on the cell cycle progression of mouse tsFT210 cells in the M phase with the MIC values of 16.4 microM (1), 4.4 microM (2), 0.45 microM (3), 4.1 microM (4), 60.8 microM (5), 26.1 microM (6) and 12.2 microM (7), respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspergillus fumigatus
  • Cell Cycle / drug effects
  • Fermentation
  • Indole Alkaloids*
  • Indoles / isolation & purification*
  • Indoles / pharmacology
  • Mice
  • Piperazines / isolation & purification*
  • Piperazines / pharmacology
  • Protein Kinases / drug effects

Substances

  • Indole Alkaloids
  • Indoles
  • Piperazines
  • demethoxyfumitremorgin C
  • tryprostatin A
  • tryprostatin B
  • Protein Kinases