Modulating the Serotonin Receptor Spectrum of Pulicatin Natural Products

Zhenjian Lin, Misty D. Smith, Gisela P. Concepcion, Margo G. Haygood, Baldomero M. Olivera, Alan Light, Eric W. Schmidt

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Serotonin (5-HT) receptors are important in health and disease, but the existence of 14 subtypes necessitates selective ligands. Previously, the pulicatins were identified as ligands that specifically bound to the subtype 5-HT2B in the 500 nM to 10 μM range and that exhibited in vitro effects on cultured mouse neurons. Here, we examined the structure-activity relationship of 30 synthetic and natural pulicatin derivatives using binding, receptor functionality, and in vivo assays. The results reveal the 2-arylthiazoline scaffold as a tunable serotonin receptor-targeting pharmacophore. Tests in mice show potential antiseizure and antinociceptive activities at high doses without motor impairment.

Original languageEnglish (US)
Pages (from-to)2360-2370
Number of pages11
JournalJournal of Natural Products
Volume80
Issue number8
DOIs
StatePublished - Aug 25 2017

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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  • Cite this

    Lin, Z., Smith, M. D., Concepcion, G. P., Haygood, M. G., Olivera, B. M., Light, A., & Schmidt, E. W. (2017). Modulating the Serotonin Receptor Spectrum of Pulicatin Natural Products. Journal of Natural Products, 80(8), 2360-2370. https://doi.org/10.1021/acs.jnatprod.7b00317