YM-254890 analogues, novel cyclic depsipeptides with Galpha(q/11) inhibitory activity from Chromobacterium sp. QS3666

Bioorg Med Chem. 2004 Jun 15;12(12):3125-33. doi: 10.1016/j.bmc.2004.04.006.


The structure elucidation and biological activity of novel YM-254890 (1) analogues and semi-synthetic derivatives are described. Three natural analogues, YM-254891 (2), YM-254892 (3), and YM-280193 (4), were isolated from the fermentation broth of Chromobacterium sp. QS3666, and two hydrogenated derivatives, YM-385780 (5) and YM-385781 (6), were synthesized from YM-254890. Their structures were determined by one- and two-dimensional NMR studies and mass spectrometry. Among these compounds, two natural analogues 2-3 which possessed acyl groups at beta-HyLeu-1 and one derivative 6 whose conformation was similar to that of 1 showed comparable Galpha(q/11) inhibitory activity to that of 1. This indicates that the acyl beta-HyLeu residue plays an important role in activity and also that the alpha,beta-unsaturated carbonyl group of the N-MeDha residue is not critical to activity. The other hydrogenated derivative 5 had significantly less activity, which could be attributed to conformational differences.

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Calcium / metabolism
  • Chromatography, High Pressure Liquid
  • Chromobacterium / chemistry*
  • GTP-Binding Protein alpha Subunits, Gq-G11 / antagonists & inhibitors*
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • Humans
  • Hydrogenation
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / isolation & purification
  • Peptides, Cyclic / pharmacology*
  • Platelet Aggregation / drug effects
  • Receptors, Purinergic P2 / metabolism
  • Receptors, Purinergic P2Y1


  • P2RY1 protein, human
  • Peptides, Cyclic
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y1
  • YM-254890
  • Adenosine Diphosphate
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Calcium