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Chemistry A European J - 2023 - Osei - The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Binuclear Copper.pdf (1.04 MB)

The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Binuclear Copper(II)-Phenanthroline Complexes

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posted on 2024-02-27, 09:55 authored by PB Osei, J Northcote-Smith, J Fang, K Singh, Fabrizio OrtuFabrizio Ortu, K Suntharalingam

Mononuclear copper(II)-phenanthroline complexes have been widely investigated as anticancer agents whereas multinuclear copper(II)-phenanthroline complexes are underexplored. Here the synthesis and characterisation of two new binuclear copper(II)-phenanthroline complexes 1 and 2 is reported, comprising of 2,9-dimethyl-1,10-phenanthroline or 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline, terminal chloride ligands, and bridging chloride or hydroxide ligands. The binuclear copper(II) complex containing 2,9-dimethyl-1,10-phenanthroline 1 displays nanomolar toxicity towards bulk breast cancer cells and breast cancer stem cells (CSCs) grown in monolayers, >50-fold greater than cisplatin (an anticancer metallodrug) and salinomycin (a gold-standard anti-CSC agent). Spectacularly, 1 exhibits >100-fold greater potency toward three-dimensionally cultured mammospheres than cisplatin and salinomycin. Mechanistic studies show that 1 evokes breast CSC apoptosis by elevating intracellular reactive oxygen species levels and damaging genomic DNA (possibly by an oxidative mechanism). To the best of our knowledge, this is the first study to probe the anti-breast CSC properties of binuclear copper(II)-phenanthroline complexes.

Funding

Immuno-chemotherapeutic Metal Complexes for Cancer Stem Cell-Directed Therapy

Engineering and Physical Sciences Research Council

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SubVAR - Sub-Valent Alkaline Earth Reagents

Engineering and Physical Sciences Research Council

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Single crystal X-ray diffractometer

Engineering and Physical Sciences Research Council

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History

Author affiliation

College of Science & Engineering/Chemistry

Version

  • VoR (Version of Record)

Published in

Chemistry - A European Journal

Volume

29

Issue

45

Pagination

e202301188

Publisher

Wiley

issn

0947-6539

eissn

1521-3765

Copyright date

2023

Available date

2024-02-27

Spatial coverage

Germany

Language

eng

Deposited by

Dr Fabrizio Ortu

Deposit date

2024-02-12

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