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Issue 7, 2016
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Iron-dependent lysosomal dysfunction mediated by a natural product hybrid

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Abstract

Artesumycin is a fluorescent hybrid of the natural products marmycin A and artemisinin. It was designed to combine the lysosomotropic properties of the angucycline and the iron-reactive capacity of the endoperoxide to target the lysosomal compartment of cancer cells. Herein, we show that artesumycin inhibits cancer cell proliferation in an iron-dependent manner and chemically fragments in vitro in the presence of redox-active iron(II). Visual detection of artesumycin by fluorescence microscopy provided substantial evidence that the small molecule selectively targets lysosomes. This original approach based on a fluorescent and iron-reactive probe represents a powerful strategy for initiating and, concomitantly, visualizing lysosomal dysfunction in human cells.

Graphical abstract: Iron-dependent lysosomal dysfunction mediated by a natural product hybrid

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Supplementary files

Article information


Submitted
08 Nov 2015
Accepted
24 Nov 2015
First published
24 Nov 2015

Chem. Commun., 2016,52, 1358-1360
Article type
Communication
Author version available

Iron-dependent lysosomal dysfunction mediated by a natural product hybrid

A. Mariani, T. T. Mai, E. Zacharioudakis, A. Hienzsch, A. Bartoli, T. Cañeque and R. Rodriguez, Chem. Commun., 2016, 52, 1358
DOI: 10.1039/C5CC09255H

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