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Synthesis and evaluation of nuciferine and roemerine enantiomers as 5-HT2 and ?1 receptor antagonists.

ABSTRACT: In this study, the (S)-enantiomers of the aporphine alkaloids, nuciferine and roemerine, were prepared via a synthetic route involving catalytic asymmetric hydrogenation and both stereoisomers were evaluated in vitro for functional activity at human 5-HT2 and adrenergic ?1 receptor subtypes using a transforming growth factor-? shedding assay. Both enantiomers of each of the compounds were found to act as antagonists at 5-HT2 and ?1 receptors. (R)-roemerine was the most potent compound at 5-HT2A and 5-HT2C receptors (pKb = 7.8-7.9) with good selectivity compared to (S)-roemerine at these two receptors and compared to its activity at 5-HT2B, ?1A, ?1B and ?1D receptors.

SUBMITTER: Heng HL

PROVIDER: S-EPMC6072365 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Synthesis and evaluation of nuciferine and roemerine enantiomers as 5-HT2 and α1 receptor antagonists.

Heng Hui Li HL Chee Chin Fei CF Chin Sek Peng SP Ouyang Yifan Y Wang Hao H Buckle Michael J C MJC Herr Deron R DR Paterson Ian C IC Doughty Stephen W SW Abd Rahman Noorsaadah N Chung Lip Yong LY

MedChemComm 20180226 3

In this study, the (S)-enantiomers of the aporphine alkaloids, nuciferine and roemerine, were prepared via a synthetic route involving catalytic asymmetric hydrogenation and both stereoisomers were evaluated in vitro for functional activity at human 5-HT2 and adrenergic α1 receptor subtypes using a transforming growth factor-α shedding assay. Both enantiomers of each of the compounds were found to act as antagonists at 5-HT2 and α1 ...[more]

PMID: 30108948

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