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Chemical constituents from Macleaya cordata (Willd) R. Br. and their phenotypic functions against a Parkinson's disease patient-derived cell line
- Source :
- Bioorganicmedicinal chemistry. 28(21)
- Publication Year :
- 2020
-
Abstract
- Cytological profiling (CP) assay against a human olfactory neuroshpere-derived (hONS) cell line using a library of traditional Chinese medicinal plant extracts gave indications that the ethanolic extract of Macleaya cordata (Willd) R. Br. elicited strong perturbations to various cellular components. Further chemical investigation of this extract resulted in the isolation of two new benzo[c]phenanthridine alkaloids, (6R)-10-methoxybocconoline (1) and 6-(1-hydroxyethyl)-10-methoxy-5,6-dihydrochelerythrine (2). Their planar structures were elucidated by extensive 1D and 2D NMR studies, together with MS data. The absolute configuration for position C-6 of 1 and relative configurations for position C-6 and C-1' of 2 were assigned by density functional theory (DFT) calculations of ECD and NMR data, respectively. Also isolated were fourteen known metabolites, including ten alkaloids (3-12) and four coumaroyl-containing compounds (13-16). Cytological profiling of the isolates against Parkinson's Disease (PD) patient-derived olfactory cells revealed bocconoline (3) and 6-(1-hydroxyethyl)-5,6-dihydrochelerythrine (4) significantly perturbated the features of cellular organelles including early endosomes, mitochondria and autophagosomes. Given that hONS cells from PD patients model some functional aspects of the disease, the results suggested that these phenotypic profiles may have a role in the mechanisms underlying PD and signified the efficacy of CP in finding potential chemical tools to study the biological pathways in PD.
- Subjects :
- Magnetic Resonance Spectroscopy
Phenotypic screening
Clinical Biochemistry
Molecular Conformation
Pharmaceutical Science
Mitochondrion
01 natural sciences
Biochemistry
Cell Line
Biological pathway
chemistry.chemical_compound
Alkaloids
Papaveraceae
Drug Discovery
Humans
Molecular Biology
Density Functional Theory
Macleaya cordata
Plants, Medicinal
biology
Phenanthridine
010405 organic chemistry
Chemistry
Plant Extracts
Circular Dichroism
Organic Chemistry
Absolute configuration
Parkinson Disease
biology.organism_classification
0104 chemical sciences
Mitochondria
010404 medicinal & biomolecular chemistry
Microscopy, Fluorescence
Cell culture
Molecular Medicine
Lysosomes
Two-dimensional nuclear magnetic resonance spectroscopy
Subjects
Details
- ISSN :
- 14643391
- Volume :
- 28
- Issue :
- 21
- Database :
- OpenAIRE
- Journal :
- Bioorganicmedicinal chemistry
- Accession number :
- edsair.doi.dedup.....9d60684b6dd24e42880c5e4fefd518c2