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

Maliszewska, Hanna K., Abdelhamid, Mahmoud A. S., Marin, Maria J. ORCID:, Waller, Zoe A. E. and Munoz-Herranz, Maria Paz ORCID: (2023) Anticancer activity and DNA interaction of bis(pyridyl)allene-derived metal complexes. Pure and Applied Chemistry, 95 (4). pp. 377-388. ISSN 0033-4545

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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.

Item Type: Article
Additional Information: Supplementary Material: This article contains supplementary material ( Research funding: Funding by the Faculty of Science (H. K. M), the School of Chemistry and the School of Pharmacy at the University of East Anglia is gratefully acknowledged. Authors would like to thank Dr Arnau del Valle (UEA) and Dr Rianne Lord (UEA) for their help with the cell culture and viability assays. Antimicrobial screening was performed by CO-ADD (Community for Antimicrobial Drug Discovery), funded by the Welcome Trust (UK) and The University of Queensland (Australia). Publisher Copyright: © 2023 IUPAC & De Gruyter. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. For more information, please visit: 2023.
Uncontrolled Keywords: dna interaction,icpoc-25,anticancer,gold carbenes,metallodrugs,chemistry(all),chemical engineering(all) ,/dk/atira/pure/subjectarea/asjc/1600
Faculty \ School: Faculty of Science > School of Chemistry
Faculty of Science > School of Pharmacy
UEA Research Groups: Faculty of Science > Research Groups > Chemistry of Life Processes
Faculty of Science > Research Groups > Chemistry of Light and Energy
Faculty of Science > Research Groups > Chemistry of Materials and Catalysis
Faculty of Science > Research Groups > Centre for Photonics and Quantum Science
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Depositing User: LivePure Connector
Date Deposited: 17 Apr 2023 17:30
Last Modified: 19 Jul 2023 01:05
DOI: 10.1515/pac-2023-0212


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