Angucyclines and Angucyclinones from Streptomyces sp. CB01913 Featuring C-Ring Cleavage and Expansion

J Nat Prod. 2015 Oct 23;78(10):2471-80. doi: 10.1021/acs.jnatprod.5b00601. Epub 2015 Sep 3.

Abstract

Angucyclines and angucyclinones are aromatic polyketides with a tetracyclic benz[a]anthracene skeleton. The benz[a]anthracene scaffold is biosynthesized by type II polyketide synthases that catalyze the decarboxylative condensation of a short acyl-CoA starter and nine extender units. Angucyclines and angucyclinones, the largest group of polycyclic aromatic polyketides, achieve structural diversity via subsequent oxidation, ring cleavage, amino acid incorporation, and glycosylation. We here report the discovery of 14 angucyclinones and two angucyclines (1-16) from Streptomyces sp. CB01913, identifying 12 new compounds featuring various oxidations on rings A and C (1, 2, and 4), different sugar moieties attached to rings A and B (3 and 6), and C-ring cleavage (5 and 10-14) and expansion (8). These new structural features, highlighted by C-ring cleavage and expansion, enrich the structural diversity of angucyclines and angucyclinones. All compounds were tested for cytotoxicity and antibacterial activities, with 1, 5, 15, and 16 showing moderate activities against selected cancer cell lines or bacterial strains.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthraquinones / chemistry
  • Anthraquinones / isolation & purification*
  • Anthraquinones / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification*
  • Antineoplastic Agents / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Streptomyces / chemistry*

Substances

  • Anthraquinones
  • Antineoplastic Agents
  • angucyclinone