Chemical constituents from Macleaya cordata (Willd) R. Br. and their phenotypic functions against a Parkinson’s disease patient-derived cell line

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Nguyen, Duy Thanh
Iqbal, Jamila
Han, Jianying
Pierens, Gregory K
Wood, Stephen A
Mellick, George D
Feng, Yunjiang
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2020
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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.

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Bioorganic & Medicinal Chemistry

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28

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21

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© 2020 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.

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Medicinal and biomolecular chemistry

Organic chemistry

Pharmacology and pharmaceutical sciences

Biochemistry and cell biology

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Nguyen, DT; Iqbal, J; Han, J; Pierens, GK; Wood, SA; Mellick, GD; Feng, Y, Chemical constituents from Macleaya cordata (Willd) R. Br. and their phenotypic functions against a Parkinson’s disease patient-derived cell line, Bioorganic & Medicinal Chemistry, 2020, 28 (21), pp. 115732

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