Iron-dependent lysosomal dysfunction mediated by a natural product hybrid. Issue 7 (8th December 2015)

• Record Type: Journal Article
• Authors: Mariani, A.; Mai, T. T.; Zacharioudakis, E.; Hienzsch, A.; Bartoli, A.; Cañeque, T.; Rodriguez, R.
• Is Part Of: Chemical communications. Volume 52:Issue 7(2016)
• Page Start: 1358
• Page End: 1360
• Publication Date: 2015-12-08
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/c5cc09255h
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : Marmycin A and artemisinin join forces as the molecular hybrid artesumycin, a new fluorescent lysosomotropic small molecule that targets lysosomal iron to kill cancer cells. 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.