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Anticancer activity and DNA interaction of bis(pyridyl)allene-derived metal complexes

Maliszewska, Hanna K; Abdelhamid, Mahmoud AS; Marín, María J; Waller, Zoë AE; Muñoz, María Paz; (2023) Anticancer activity and DNA interaction of bis(pyridyl)allene-derived metal complexes. Pure and Applied Chemistry 10.1515/pac-2023-0212. (In press). Green open access

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Abstract

The constant need for novel drugs has prompted the scientific community to explore alternative structures to natural products and small and medium size organic compounds used in classic medicinal and pharmaceutical chemistry. Since the discovery of cisplatin, organometallic compounds have revealed great potential as metallodrugs and their development has exponentially grown in recent years. In this manuscript, we describe our efforts towards the synthesis of new metallodrugs by reaction of bis(pyridyl)allenes and metal complexes. Two classes of compounds are presented: one in which the allene structure is intact and the metal (Pd(II), Pt(IV) or Au(III)) coordinates to the pyridine-nitrogens; and another, in which one of the pyridines cyclises into a gold-activated allene to form β-N-stabilised gold carbenes. Both classes of compounds are active catalysts in important organic reactions, and are also promising antimicrobial, antifungal and anticancer agents. In this work, we describe the promising anticancer activity, against breast cancer cells, of the gold carbene complexes, and preliminary studies of their interaction with DNA, including non-canonical DNA structures. Our results have revealed an unusual selective stabilisation of hTeloC i-motif by one of the Au(III) carbene complexes, that opens up exciting opportunities for further development of novel DNA-binding metallodrugs.

Type: Article
Title: Anticancer activity and DNA interaction of bis(pyridyl)allene-derived metal complexes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1515/pac-2023-0212
Publisher version: https://doi.org/10.1515/pac-2023-0212
Language: English
Additional information: © 2023 IUPAC & De Gruyter. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. For more information, please visit: http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: anticancer; DNA interaction; gold carbenes; ICPOC-25; metallodrugs
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10170010
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