Modulating the Serotonin Receptor Spectrum of Pulicatin Natural Products

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

Research output: Contribution to journalArticle

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
Externally publishedYes

Fingerprint

Serotonin Receptors
Biological Products
Ligands
Structure-Activity Relationship
Scaffolds
Neurons
Assays
Serotonin
Health
Derivatives
serotonin 5 receptor
In Vitro Techniques

ASJC Scopus subject areas

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

Cite this

Lin, Z., Smith, M. D., Concepcion, G. P., Haygood, M., 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

Modulating the Serotonin Receptor Spectrum of Pulicatin Natural Products. / Lin, Zhenjian; Smith, Misty D.; Concepcion, Gisela P.; Haygood, Margo; Olivera, Baldomero M.; Light, Alan; Schmidt, Eric W.

In: Journal of Natural Products, Vol. 80, No. 8, 25.08.2017, p. 2360-2370.

Research output: Contribution to journalArticle

Lin, Z, Smith, MD, Concepcion, GP, Haygood, M, Olivera, BM, Light, A & Schmidt, EW 2017, 'Modulating the Serotonin Receptor Spectrum of Pulicatin Natural Products', Journal of Natural Products, vol. 80, no. 8, pp. 2360-2370. https://doi.org/10.1021/acs.jnatprod.7b00317
Lin Z, Smith MD, Concepcion GP, Haygood M, Olivera BM, Light A et al. Modulating the Serotonin Receptor Spectrum of Pulicatin Natural Products. Journal of Natural Products. 2017 Aug 25;80(8):2360-2370. https://doi.org/10.1021/acs.jnatprod.7b00317
Lin, Zhenjian ; Smith, Misty D. ; Concepcion, Gisela P. ; Haygood, Margo ; Olivera, Baldomero M. ; Light, Alan ; Schmidt, Eric W. / Modulating the Serotonin Receptor Spectrum of Pulicatin Natural Products. In: Journal of Natural Products. 2017 ; Vol. 80, No. 8. pp. 2360-2370.
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