Pulicatins A-E, neuroactive thiazoline metabolites from cone snail-associated bacteria

J Nat Prod. 2010 Nov 29;73(11):1922-6. doi: 10.1021/np100588c. Epub 2010 Oct 28.

Abstract

The cone snail Conus pulicarius from the Philippines provides a specific habitat for actinomycetes and other bacteria. A phenotypic screen using primary cultures of mouse dorsal root ganglion neurons revealed that one C. pulicarius associate, Streptomyces sp. CP32, produces a series of natural products that enhance or diminish whole-cell Ca(2+) flux. These compounds include known thiazoline compounds and a series of new derivatives, pulicatins A-E (6-10). Individual compounds were shown to bind to a series of human receptors, with selective binding to the human serotonin 5-HT(2B) receptor. Here, we report the structure elucidation of the new compounds and results of the neurological assays.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actinobacteria / growth & development
  • Animals
  • Calcium / metabolism
  • Conus Snail / microbiology*
  • Humans
  • Mice
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Philippines
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism
  • Receptor, Serotonin, 5-HT2B / metabolism
  • Serotonin / metabolism
  • Streptomyces / chemistry
  • Streptomyces / growth & development
  • Thiazolidines / chemistry
  • Thiazolidines / isolation & purification*
  • Thiazolidines / pharmacology*

Substances

  • Receptor, Serotonin, 5-HT2B
  • Thiazolidines
  • Serotonin
  • Calcium