Frontispiece: NMR Fingerprints of the Drug-like Natural-Product Space Identify IotrochotazineA: A Chemical Probe to Study Parkinson's Disease

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 patter...

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Veröffentlicht in:Angewandte Chemie International Edition 2014-06, Vol.53 (24), p.np-np
Hauptverfasser: Grkovic, Tanja, Pouwer, Rebecca H, Vial, Marie-Laure, Gambini, Luca, Noel, Alba, Hooper, John N A, Wood, Stephen A, Mellick, George D, Quinn, Ronald J
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Sprache:eng
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Zusammenfassung: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, iotrochotazineA (1), sourced from an Australian marine sponge Iotrochotasp. 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 1μM was not cytotoxic but specifically affected the morphology and cellular distribution of lysosomes and early endosomes.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201482471