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

doi:10.1021/acs.jnatprod.7b00317

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 journal › Article › peer-review

6 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-HT_2B 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 language	English (US)
Pages (from-to)	2360-2370
Number of pages	11
Journal	Journal of Natural Products
Volume	80
Issue number	8
DOIs	https://doi.org/10.1021/acs.jnatprod.7b00317
State	Published - 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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10.1021/acs.jnatprod.7b00317

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title = "Modulating the Serotonin Receptor Spectrum of Pulicatin Natural Products",

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.",

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AU - Lin, Zhenjian

AU - Smith, Misty D.

AU - Concepcion, Gisela P.

AU - Haygood, Margo G.

AU - Olivera, Baldomero M.

AU - Light, Alan

AU - Schmidt, Eric W.

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AB - 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.

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Modulating the Serotonin Receptor Spectrum of Pulicatin Natural Products

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