11-Deoxylandomycinone and landomycins X-Z, new cytotoxic angucyclin(on)es from a Streptomyces cyanogenus K62 mutant strain

J Antibiot (Tokyo). 2011 Jan;64(1):141-50. doi: 10.1038/ja.2010.121. Epub 2010 Oct 27.

Abstract

Four new angucyclin(on)es, 11-deoxylandomycinone (1) and landomycins X-Z (2-4) were isolated from the crude extract of Streptomyces cyanogenus K62 mutant strain, along with the recently reported landomycins S, T and V (5-7) and five other known compounds. The structures of the new compounds 1-4 were elucidated by 1D and 2D NMR studies along with HR-MS analyses. Unique about the structures is that the fourth sugar moiety (sugar D) in landomycins X-Z (2-4) was β-D-amicetose instead of β-D-olivose, usually found in this position. The new angucyclin(on)es were biologically evaluated in comparison with previously known congeners against a small panel of MCF-7 (estrogen responsive) and MDA 231 (estrogen refractory) breast cancer cell lines. 11-deoxylandomycinone (IC(50) 2.1 ± 0.3 and 1.2 ± 0.4 μM) and landomycin Y (IC(50) 1.0 ± 0.1 and 2.0 ± 0.1 μM) showed the highest cytotoxic potencies against both the cell lines.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aminoglycosides / chemistry
  • Aminoglycosides / isolation & purification*
  • Aminoglycosides / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytotoxins / chemistry
  • Cytotoxins / isolation & purification*
  • Cytotoxins / pharmacology
  • Deoxy Sugars / chemistry
  • Deoxy Sugars / isolation & purification*
  • Deoxy Sugars / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Nuclear Magnetic Resonance, Biomolecular
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Ultraviolet
  • Streptomyces / genetics
  • Streptomyces / metabolism*

Substances

  • Aminoglycosides
  • Antineoplastic Agents
  • Cytotoxins
  • Deoxy Sugars