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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 ?M 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.

SUBMITTER: Lin Z

PROVIDER: S-EPMC6025773 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Modulating the Serotonin Receptor Spectrum of Pulicatin Natural Products.

Lin Zhenjian Z Smith Misty D MD Concepcion Gisela P GP Haygood Margo G MG Olivera Baldomero M BM Light Alan A Schmidt Eric W EW

Journal of natural products 20170726 8

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<sub>2B</sub> 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 r ...[more]

PMID: 28745513

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