title: A Grand Challenge: Unbiased Phenotypic Function of Metabolites from Jaspis splendens against Parkinson's Disease.
abstract: 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.
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: Yunjiang
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: Mariyam
authors.initials: M
authors.lastname: Murtaza
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Wood
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: George
authors.initials: G
authors.lastname: Mellick
authors.affiliation: Queensland Museum , South Brisbane, QLD 4101, Australia.
authors.forename: John N A
authors.initials: JN
authors.lastname: Hooper
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
mesh_terms: D000818:Animals; D047630:Depsipeptides; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D010300:Parkinson Disease / Q000188:drug therapy*; D011161:Porifera / Q000737:chemistry*
chemical_list: D047630:Depsipeptides; D026121:Indole Alkaloids; C057531:jasplakinolide