A Grand Challenge: Unbiased Phenotypic Function of Metabolites from Jaspis splendens against Parkinson's Disease

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Author(s)
Wang, Dongdong
Feng, Yunjiang
Murtaza, Mariyam
Wood, Stephen
Mellick, George
Hooper, John NA
Quinn, Ronald J
Year published
2016
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A grand challenge in natural product chemistry is to determine the biological effects of all natural products. A phenotypic approach is frequently used for determining the activity of a compound and its potential impact on a disease state. Chemical investigation of a specimen of Jaspis splendens collected from the Great Barrier Reef resulted in the isolation of a new pterin derivative, jaspterin (1), a new bisindole alkaloid, splendamide (2), and a new imidazole alkaloid, jaspnin A (3) TFA salt. Jaspamycin (8) and 6-bromo-1H-indole-3-carboximidamide (16) are reported for the first time as naturally occurring metabolites. ...
View more >A grand challenge in natural product chemistry is to determine the biological effects of all natural products. A phenotypic approach is frequently used for determining the activity of a compound and its potential impact on a disease state. Chemical investigation of a specimen of Jaspis splendens collected from the Great Barrier Reef resulted in the isolation of a new pterin derivative, jaspterin (1), a new bisindole alkaloid, splendamide (2), and a new imidazole alkaloid, jaspnin A (3) TFA salt. Jaspamycin (8) and 6-bromo-1H-indole-3-carboximidamide (16) are reported for the first time as naturally occurring metabolites. Known nucleosides (4–7, 9, 10), aglycones (11–13), indole alkaloids (14, 15, 17), and jaspamide peptides (18–22) were also isolated. The structures of the three new compounds 1–3 were unambiguously elucidated based on NMR and mass spectroscopic data. Jaspnin A (3) contained a rare thiomethylated imidazolinium unit. Coupling an unbiased phenotypic assay using a human olfactory neurosphere-derived cell model of Parkinson’s disease to all of the natural products from the species J. splendens allowed the phenotypic profiles of the metabolites to be investigated.
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View more >A grand challenge in natural product chemistry is to determine the biological effects of all natural products. A phenotypic approach is frequently used for determining the activity of a compound and its potential impact on a disease state. Chemical investigation of a specimen of Jaspis splendens collected from the Great Barrier Reef resulted in the isolation of a new pterin derivative, jaspterin (1), a new bisindole alkaloid, splendamide (2), and a new imidazole alkaloid, jaspnin A (3) TFA salt. Jaspamycin (8) and 6-bromo-1H-indole-3-carboximidamide (16) are reported for the first time as naturally occurring metabolites. Known nucleosides (4–7, 9, 10), aglycones (11–13), indole alkaloids (14, 15, 17), and jaspamide peptides (18–22) were also isolated. The structures of the three new compounds 1–3 were unambiguously elucidated based on NMR and mass spectroscopic data. Jaspnin A (3) contained a rare thiomethylated imidazolinium unit. Coupling an unbiased phenotypic assay using a human olfactory neurosphere-derived cell model of Parkinson’s disease to all of the natural products from the species J. splendens allowed the phenotypic profiles of the metabolites to be investigated.
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Journal Title
Journal of Natural Products
Volume
79
Issue
2
Copyright Statement
© 2016 The American Chemical Society and American Society of Pharmacognosy. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
Subject
Chemical sciences
Biological sciences
Biomedical and clinical sciences
Traditional, complementary and integrative medicine