Synthesis and evaluation of nuciferine and roemerine enantiomers as 5-HT2 and α1 receptor antagonists
Document Type
Article
Publication Date
1-1-2018
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 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 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, α1A, α1B and α1D receptors.
Keywords
biosynthesis, catalysis, enantiomer, human, hydrogenation, in vitro study, isomer, priority journal, protein function, stereoselectivity
Divisions
Dentistry,fac_med,CHEMISTRY
Funders
Ministry of Science, Technology and Innovation, Malaysia (02-01-03-SF0937),Ministry of Higher Education, Malaysia, High Impact Research Grant (HIR-MoHE: UM.C/625/1/HIR/MOHE/MED/17 & UM.C/625/1/HIR/MOHE/MED/33)
Publication Title
MedChemComm
Volume
9
Issue
3
Publisher
Royal Society of Chemistry