Angucycline Glycosides from an Intertidal Sediments Strain Streptomyces sp. and Their Cytotoxic Activity against Hepatoma Carcinoma Cells

Mar Drugs. 2018 Nov 27;16(12):470. doi: 10.3390/md16120470.

Abstract

Four angucycline glycosides including three new compounds landomycin N (1), galtamycin C (2) and vineomycin D (3), and a known homologue saquayamycin B (4), along with two alkaloids 1-acetyl-β-carboline (5) and indole-3-acetic acid (6), were isolated from the fermentation broth of an intertidal sediments-derived Streptomyces sp. Their structures were established by IR, HR-ESI-MS, 1D and 2D NMR techniques. Among the isolated angucyclines, saquayamycin B (4) displayed potent cytotoxic activity against hepatoma carcinoma cells HepG-2, SMMC-7721 and plc-prf-5, with IC50 values 0.135, 0.033 and 0.244 μM respectively, superior to doxorubicin. Saquayamycin B (4) also induced apoptosis in SMMC-7721 cells as detected by its morphological characteristics in 4',6-diamidino-2-phenylindole (DAPI) staining experiment.

Keywords: SMMC-7721; Streptomyces; angucycline glycosides; apoptosis; cytotoxicity; saquayamycin.

MeSH terms

  • Anthracyclines / chemistry
  • Anthracyclines / isolation & purification
  • Anthracyclines / pharmacology*
  • Anthracyclines / therapeutic use
  • Anthraquinones / chemistry
  • Anthraquinones / isolation & purification
  • Anthraquinones / pharmacology
  • Anthraquinones / therapeutic use
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / drug therapy
  • Drug Screening Assays, Antitumor
  • Geologic Sediments / microbiology*
  • Hep G2 Cells
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Proton Magnetic Resonance Spectroscopy
  • Spectrometry, Mass, Electrospray Ionization
  • Streptomyces / metabolism*

Substances

  • Anthracyclines
  • Anthraquinones
  • Antineoplastic Agents
  • saquayamycin B