Isolation and characterization of novel geldanamycin analogues

J Antibiot (Tokyo). 2004 Jul;57(7):421-8. doi: 10.7164/antibiotics.57.421.

Abstract

New geldanamycin analogues with novel structures arising from direct microbial bioconversion and a genetically engineered geldanamycin producer were isolated and characterized. Three compounds, 15-hydroxygeldanamycin, a tricyclic geldanamycin analog (KOSN-1633), and methyl-geldanamycinate), were isolated after geldanamycin was added to a growing culture of the herbimycin producing strain-Streptomyces hygroscopicus AM-3672. Two related compounds, 17-formyl-17-demethoxy-18-O,-21-O-dihydrogeldanamycin and 17-hydroxymethyl-17-demethoxygeldanamycin were isolated from S. hygroscopicus NRRL 3602/pKOS279-78, a geldanamycin-producing strain containing various genes isolated from S. hygroscopicus AM-3672. Compared with geldanamycin, these five new compounds exhibited reduced cytotoxicity against SKBr3 cancer cells.

MeSH terms

  • Antibiotics, Antineoplastic / isolation & purification*
  • Antibiotics, Antineoplastic / pharmacology
  • Benzoquinones
  • Cell Line, Tumor
  • Humans
  • Lactams, Macrocyclic
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Quinones / metabolism*
  • Quinones / pharmacology
  • Streptomyces / metabolism*
  • Structure-Activity Relationship

Substances

  • Antibiotics, Antineoplastic
  • Benzoquinones
  • Lactams, Macrocyclic
  • Quinones
  • geldanamycin