University of Oulu

Cite this: DaltonTrans., 2021, 50, 17413, https://doi.org/10.1039/D1DT02783B

Cancer molecular biology and strategies for the design of cytotoxic gold(i) and gold(iii) complexes : a tutorial review

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Author: van der Westhuizen, Danielle1; Bezuidenhout, Daniela I.2; Munro, Orde Q.1
Organizations: 1Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, Johannesburg 2050, South Africa
2Laboratory of Inorganic Chemistry, Environmental and Chemical Engineering, University of Oulu, P. O. Box 3000, 90014 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 9.6 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe202201051216
Language: English
Published: Royal Society of Chemistry, 2021
Publish Date: 2022-01-05
Description:

Abstract

This tutorial review highlights key principles underpinning the design of selected metallodrugs to target specific biological macromolecules (DNA and proteins). The review commences with a descriptive overview of the eukaryotic cell cycle and the molecular biology of cancer, particularly apoptosis, which is provided as a necessary foundation for the discovery, design, and targeting of metal-based anticancer agents. Drugs which target DNA have been highlighted and clinically approved metallodrugs discussed. A brief history of the development of mainly gold-based metallodrugs is presented prior to addressing ligand systems for stabilizing and adding functionality to bio-active gold(I) and gold(III) complexes, particularly in the burgeoning field of anticancer metallodrugs. Concepts such as multi-modal and selective cytotoxic agents are covered where necessary for selected compounds. The emerging role of carbenes as the ligand system of choice to achieve these goals for gold-based metallodrug candidates is highlighted prior to closing the review with comments on some future directions that this research field might follow. The latter section ultimately emphasizes the importance of understanding the fate of metal complexes in cells to garner key mechanistic insights.

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Series: Dalton transactions
ISSN: 1477-9226
ISSN-E: 1477-9234
ISSN-L: 1477-9226
Volume: 50
Issue: 47
Pages: 17413 - 17437
DOI: 10.1039/d1dt02783b
OADOI: https://oadoi.org/10.1039/d1dt02783b
Type of Publication: A2 Review article in a scientific journal
Field of Science: 116 Chemical sciences
1182 Biochemistry, cell and molecular biology
Subjects:
Funding: The authors (DvdW and DIB) gratefully acknowledge financial support from the National Research Foundation (NRF), South Africa (grant numbers: NRF 108521, NRF 1057404, and NRF 105529). OQM thanks the South African Research Chairs Initiative of the Department of Science and Innovation and NRF of South Africa (SARChI grant number 64799) for generous financial support and the University of the Witwatersrand. DIB thanks the University of Oulu for current financial support.
Copyright information: © The Royal Society of Chemistry 2020. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
  https://creativecommons.org/licenses/by/3.0/