Natural quinones and their analogues: synthesis, intracellular redox cycling and identification of indoleamine-2,3-dioxygenase (IDO) as a potential target for anticancer activity

Blunt, Christopher and Torcuk, Canan and Liu, Yang and Lewis, William and Siegel, David and Ross, David and Moody, Christopher J. (2015) Natural quinones and their analogues: synthesis, intracellular redox cycling and identification of indoleamine-2,3-dioxygenase (IDO) as a potential target for anticancer activity. Angewandte Chemie International Edition, 54 (30). pp. 8740-8745. ISSN 1521-3773

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Abstract

Natural quinones, often linked with cellular oxidation processes, also exhibit pronounced biological activity. In particular, the structurally unique isothiazolo-naphthoquinone, aulosirazole, isolated from blue-green alga, possesses selective antitumor cytotoxicity, although its mechanism of action is unknown. The first synthesis of aulosirazole is now described, using a route centered upon a late stage regioselective Diels-Alder reaction. The structurally related natural product pronqodine A, an inhibitor of prostaglandin release, and analogues thereof, were also prepared for comparison. Biological evaluation of the compounds identified one potential target as the immunoregulatory enzyme indoleamine-2,3-dioxygenase (IDO). The isothiazolo-quinones are also efficient substrates for the human quinone reductase NQO1, and undergo intracellular NQO1-dependent redox cycling resulting in the generation of reactive oxygen species, and at lower doses have the potential to alter the ratio of intracellular oxidized to reduced pyridine nucleotides.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: Blunt, C. E., Torcuk, C., Liu, Y., Lewis, W., Siegel, D., Ross, D. and Moody, C. J. (2015), Synthesis and Intracellular Redox Cycling of Natural Quinones and Their Analogues and Identification of Indoleamine-2,3-dioxygenase (IDO) as Potential Target for Anticancer Activity. Angew. Chem. Int. Ed., 54: 8740–8745. doi:10.1002/anie.201503323 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/anie.201503323/abstract
Schools/Departments: University of Nottingham UK Campus > Faculty of Science > School of Chemistry
Identification Number: https://doi.org/10.1002/anie.201503323
Depositing User: Bramwell, Roseanna
Date Deposited: 17 Nov 2015 14:54
Last Modified: 24 Sep 2016 21:54
URI: http://eprints.nottingham.ac.uk/id/eprint/30847

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