Natural quinones and their analogues: synthesis, intracellular redox cycling and identification of indoleamine-2,3-dioxygenase (IDO) as a potential target for anticancer activity
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...
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Wiley-VCH Verlag
2015
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| Online Access: | https://eprints.nottingham.ac.uk/30847/ |
| _version_ | 1848794075209138176 |
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| author | Blunt, Christopher Torcuk, Canan Liu, Yang Lewis, William Siegel, David Ross, David Moody, Christopher J. |
| author_facet | Blunt, Christopher Torcuk, Canan Liu, Yang Lewis, William Siegel, David Ross, David Moody, Christopher J. |
| author_sort | Blunt, Christopher |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:10:25Z |
| format | Article |
| id | nottingham-30847 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:10:25Z |
| publishDate | 2015 |
| publisher | Wiley-VCH Verlag |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-308472020-05-04T17:11:00Z https://eprints.nottingham.ac.uk/30847/ 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 Torcuk, Canan Liu, Yang Lewis, William Siegel, David Ross, David Moody, Christopher J. 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. Wiley-VCH Verlag 2015-06-10 Article PeerReviewed Blunt, Christopher, Torcuk, Canan, Liu, Yang, Lewis, William, Siegel, David, 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 http://onlinelibrary.wiley.com/doi/10.1002/anie.201503323/abstract doi:10.1002/anie.201503323 doi:10.1002/anie.201503323 |
| spellingShingle | Blunt, Christopher Torcuk, Canan Liu, Yang Lewis, William Siegel, David Ross, David Moody, Christopher J. Natural quinones and their analogues: synthesis, intracellular redox cycling and identification of indoleamine-2,3-dioxygenase (IDO) as a potential target for anticancer activity |
| title | Natural quinones and their analogues: synthesis, intracellular redox cycling and identification of indoleamine-2,3-dioxygenase (IDO) as a potential target for anticancer activity |
| title_full | Natural quinones and their analogues: synthesis, intracellular redox cycling and identification of indoleamine-2,3-dioxygenase (IDO) as a potential target for anticancer activity |
| title_fullStr | Natural quinones and their analogues: synthesis, intracellular redox cycling and identification of indoleamine-2,3-dioxygenase (IDO) as a potential target for anticancer activity |
| title_full_unstemmed | Natural quinones and their analogues: synthesis, intracellular redox cycling and identification of indoleamine-2,3-dioxygenase (IDO) as a potential target for anticancer activity |
| title_short | Natural quinones and their analogues: synthesis, intracellular redox cycling and identification of indoleamine-2,3-dioxygenase (IDO) as a potential target for anticancer activity |
| title_sort | natural quinones and their analogues: synthesis, intracellular redox cycling and identification of indoleamine-2,3-dioxygenase (ido) as a potential target for anticancer activity |
| url | https://eprints.nottingham.ac.uk/30847/ https://eprints.nottingham.ac.uk/30847/ https://eprints.nottingham.ac.uk/30847/ |