Landomycins P-W, cytotoxic angucyclines from streptomyces cyanogenus S-136

Khaled A. Shaaban, Sowmyalakshmi Srinivasan, Raj Kumar, Chendil Damodaran, Jürgen Rohr

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Streptomyces cyanogenus S-136 is the producer of previously reported landomycins A-D. An analysis of minor products of the strain led to isolation and structure elucidation of eight new congeners, named landomycins P-W (5, 6, 3, 17, 9, 10, 15, 7), along with 10 other known angucyclin(on)es. The structures of the new compounds were established from their NMR and mass spectrometry data. The activity of these angucyclin(on)es was determined using MCF-7 (estrogen responsive) and MDA-231 (estrogen refractory) breast cancer cell lines. Cell viability assays showed that anhydrolandomycinone (2), landomycinone (11), and landomycin A (16) showed the best combined activities in both MCF-7 and MDA-231 assays, with 2 being the most potent in the former and 11 and 16 in the latter. These data reveal that some of the aglycones are equipotent to the principle product 16, which contains the longest saccharide chain. Specifically, anhydrolandomycinone (2) was the most active against MCF-7 cells (IC 50 ) 1.8 μM). Compounds with shorter saccharidal moieties were less potent against MCF-7. The fact that the most active landomycins have either long penta- or hexasaccharide chains or no sugars at all suggests that the large compounds may act by a different mode of action than their small sugar-free congeners. The results presented here provide more insights into the structure-activity relationship of landomycins.

Original languageEnglish
Pages (from-to)2-11
Number of pages10
JournalJournal of Natural Products
Volume74
Issue number1
DOIs
StatePublished - Jan 28 2011

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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