Andrade, Késsia HS;
Coelho, Jaime AS;
Frade, Raquel;
Madureira, Ana M;
Nunes, João PM;
Caddick, Stephen;
Gomes, Rafael Filipe Arbuez;
(2023)
Functionalized Cyclopentenones with Low Electrophilic Character as Anticancer Agents.
ChemMedChem
, 18
(13)
, Article e202300104. 10.1002/cmdc.202300104.
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Abstract
In this study were synthesized non-Michael acceptor cyclopentenones (CP) from biomass derivative furfural as anticancer agents. Cyclic enones, both from natural sources and synthetic analogues, have been described as cytotoxic agents. Most of these agents were unsuccessful in becoming valuable therapeutic agents due to toxicity problems derived from unselective critical biomacromolecule alkylation. This may be caused by Michael addition to the enone system. Ab initio studies revealed that 2,4-substituted CPs are less prone to Michael additions, and as such were tested three families of those derivatives. We prepare the new CPs from furfural through a tandem furan ring opening/nazarov electrocyclization and further functionalization. Experimentally the 2,4-substituted CPs exhibited no reactivity towards sulphur nucleophiles, while maintaining cytotoxicity against HT-29, MCF-7, NCI-H460, HCT-116 and MDA-MB 231 cells lines. Moreover, the selected CP are non-toxic against healthy HEK 293T cell lines and present proper calculated drug-like properties.
| Type: | Article |
|---|---|
| Title: | Functionalized Cyclopentenones with Low Electrophilic Character as Anticancer Agents |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/cmdc.202300104 |
| Publisher version: | http://doi.org/10.1002/cmdc.202300104 |
| Language: | English |
| Additional information: | © 2023 The Authors. ChemMedChem published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
| Keywords: | biomass, cancer, cyclopentenone, medicinal chemistry, sustainable chemistry |
| 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-pp.ucl.ac.uk/id/eprint/10169889 |
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