NMR fingerprints of the drug-like natural-product space identify iotrochotazine A: a chemical probe to study Parkinson's disease.

Abstract

The NMR spectrum of a mixture of small molecules is a fingerprint of all of its components. Herein, we present an NMR fingerprint method that takes advantage of the fact that fractions contain simplified NMR profiles, with minimal signal overlap, to allow the identification of unique spectral patterns. The approach is exemplified in the identification of a novel natural product, iotrochotazine A (1), sourced from an Australian marine sponge Iotrochota sp. Compound 1 was used as a chemical probe in a phenotypic assay panel based on human olfactory neurosphere-derived cells (hONS) from idiopathic Parkinson's disease patients. Compound 1 at 1 μM was not cytotoxic but specifically affected the morphology and cellular distribution of lysosomes and early endosomes.

• Authors: Tanja Grkovic, Rebecca H Pouwer, Marie-Laure Vial, Luca Gambini, Alba Noël, John N A Hooper, Stephen A Wood, George D Mellick, Ronald J Quinn
• Journal: Angewandte Chemie (International ed. in English) (Angew Chem Int Ed Engl) Vol. 53 Issue 24 Pg. 6070-4 (Jun 10 2014) ISSN: 1521-3773 [Electronic] Germany
• PMID: 24737726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Biological Products
• Heterocyclic Compounds, 3-Ring
• iotrochotazine A

Topics

• Animals
• Biological Products (chemistry)
• Heterocyclic Compounds, 3-Ring (chemistry, pharmacology)
• Humans
• Molecular Structure
• Nuclear Magnetic Resonance, Biomolecular (methods)
• Olfactory Mucosa (drug effects, pathology)
• Parkinson Disease (diagnosis, pathology)
• Porifera (chemistry)