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

J Nat Prod. 2016 Feb 26;79(2):353-61. doi: 10.1021/acs.jnatprod.5b00987. Epub 2016 Feb 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Depsipeptides
  • Drug Screening Assays, Antitumor
  • Humans
  • Indole Alkaloids / chemistry
  • Indole Alkaloids / isolation & purification*
  • Indole Alkaloids / pharmacology*
  • Molecular Structure
  • Parkinson Disease / drug therapy*
  • Porifera / chemistry*

Substances

  • Depsipeptides
  • Indole Alkaloids
  • jasplakinolide