Westhuizen, D, Slabber, CA, Fernandes, MA et al. (6 more authors) (2021) A Cytotoxic Bis(1,2,3‐triazol‐5‐ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation. Chemistry – A European Journal, 27 (32). pp. 8295-8307. ISSN 0947-6539
Abstract
The syntheses of bis(triazolium)carbazole precursors and their corresponding coinage metal (Au, Ag) complexes are reported. For alkylated triazolium salts, di- or tetranuclear complexes with bridging ligands were isolated, while the bis(aryl) analogue afforded a bis(carbene) AuI-CNC pincer complex suitable for oxidation to the redox-stable [AuIII(CNC)Cl]+ cation. Although the ligand salt and the [AuIII(CNC)Cl]+ complex were both notably cytotoxic toward the breast cancer cell line MDA-MB-231, the AuIII complex was somewhat more selective. Electrophoresis, viscometry, UV-vis, CD and LD spectroscopy suggest the cytotoxic [AuIII(CNC)Cl]+ complex behaves as a partial DNA intercalator. In silico screening indicated that the [AuIII(CNC)Cl]+ complex can target DNA three-way junctions with good specificity, several other regular B-DNA forms, and Z-DNA. Multiple hydrophobic π-type interactions involving T and A bases appear to be important for B-form DNA binding, while phosphate O⋅⋅⋅Au interactions evidently underpin Z-DNA binding. The CNC ligand effectively stabilizes the AuIII ion, preventing reduction in the presence of glutathione. Both the redox stability and DNA affinity of the hit compound might be key factors underpinning its cytotoxicity in vitro.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Physical Chemistry (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 08 Jun 2023 12:51 |
Last Modified: | 08 Jun 2023 12:51 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/chem.202100598 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:199883 |