Telomerase inhibitors from cyanobacteria: isolation and synthesis of sulfoquinovosyl diacylglycerols from Microcystis aeruguinosa PCC 7806

Chemistry. 2013 Apr 2;19(14):4596-601. doi: 10.1002/chem.201203296. Epub 2013 Jan 31.

Abstract

By using the Telospot assay, 27 different extracts of cyanobacteria were evaluated for telomerase inhibition. All extracts showed varying, but significant activity. We selected Microcystis aeruguinosa PCC 7806 to identify the active compound and a bioassay guided fractionation led us to isolate mixtures of sulfoquinovosyl diacylglycerols (SQDGs), which were identified by 2D NMR and MS/MS experiments. Pure SQDG derivatives were then synthesized. The IC(50) values of pure synthetic sulfoquinovosyl dipalmitoylglycerol and the monopalmitoylated derivative against telomerase were determined to be 17 and 40 μM, respectively. A structure-activity relationship study allowed the identification of compounds with modified lipophilic acyl groups that display improved activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diglycerides / chemical synthesis*
  • Diglycerides / chemistry
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Glycolipids / chemical synthesis*
  • Glycolipids / chemistry
  • Microcystis / metabolism*
  • Phencyclidine / analogs & derivatives
  • Structure-Activity Relationship
  • Tandem Mass Spectrometry
  • Telomerase / antagonists & inhibitors*
  • Telomerase / metabolism

Substances

  • Diglycerides
  • Enzyme Inhibitors
  • Glycolipids
  • sulfoquinovosyl diglyceride
  • 1-piperidinocyclohexanecarbonitrile
  • Telomerase
  • Phencyclidine