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- Title
The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Binuclear Copper(II)‐Phenanthroline Complexes.
- Authors
Osei, Priscilla B.; Northcote‐Smith, Joshua; Fang, Jiaxin; Singh, Kuldip; Ortu, Fabrizio; Suntharalingam, Kogularamanan
- Abstract
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.
- Subjects
CANCER stem cells; CANCER cells; BREAST cancer; COPPER chlorides; COPPER; REACTIVE oxygen species; COMPREHENSION in children; LIGANDS (Chemistry)
- Publication
Chemistry - A European Journal, 2023, Vol 29, Issue 45, p1
- ISSN
0947-6539
- Publication type
Article
- DOI
10.1002/chem.202301188