UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Monocyclic Quinone Structure-Activity Patterns: Synthesis of Catalytic Inhibitors of Topoisomerase II with Potent Anti-Proliferative Activity

Marson, C; Waugh, T; Masters, J; Aliev, A; (2020) Monocyclic Quinone Structure-Activity Patterns: Synthesis of Catalytic Inhibitors of Topoisomerase II with Potent Anti-Proliferative Activity. ChemMedChem , 15 (1) pp. 114-124. 10.1002/cmdc.201900548. Green open access

[thumbnail of Article]
Preview
Text (Article)
Quinones Paper (Accepted Version) Marson.pdf - Accepted Version

Download (4MB) | Preview
[thumbnail of Supplementary Materal]
Preview
Text (Supplementary Materal)
Quinone Anti-Cancer Agents Supporting Information Marson.pdf - Accepted Version

Download (2MB) | Preview

Abstract

The monocyclic 1,4-benzoquinone, HU-331, the direct oxidation product of cannabidiol, inhibits the catalytic activity of topoisomerase II but without inducing DNA strand breaks or generating free radicals, and unlike many fused-ring quinones exhibits minimal cardiotoxicity. Thus, monocyclic quinones have potential as anti-cancer agents, and investigation of the structural origins of their biological activity is warranted. New syntheses of cannabidiol and (±)-HU-331 are here reported. Integrated synthetic protocols afforded a wide range of polysubstituted resorcinol derivatives; many of the corresponding novel 2-hydroxy-1,4-benzoquinone derivatives are potent inhibitors of the catalytic activity of topoisomerase II, some more so than HU-331, whose monoterpene unit replaced by a 3-cycloalkyl unit conferred increased anti-proliferative properties in cell lines with IC50 values extending below 1 mM, and greater stability in solution than HU-331. The principal pharmacophore of quinones related to HU-331 was identified. Selected monocyclic quinones show potential for the development of new anticancer agents.

Type: Article
Title: Monocyclic Quinone Structure-Activity Patterns: Synthesis of Catalytic Inhibitors of Topoisomerase II with Potent Anti-Proliferative Activity
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/cmdc.201900548
Publisher version: https://doi.org/10.1002/cmdc.201900548
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: anti-cancer agents, cannabidiol, Frémy's salt, HU-331, monocyclic quinones, structure-activity relationships
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10085689
Downloads since deposit
267Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item