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Polypyridyl Zinc(II)-Indomethacin Complexes with Potent Anti-Breast Cancer Stem Cell Activity

Department of Chemistry, King’s College London, London SE1 1DB, UK
Author to whom correspondence should be addressed.
Molecules 2018, 23(9), 2253;
Received: 17 August 2018 / Revised: 27 August 2018 / Accepted: 31 August 2018 / Published: 4 September 2018
(This article belongs to the Special Issue Metal Complexes of Biological Ligands)
Cancer stem cells (CSCs) are thought of as a clinically pertinent subpopulation of tumors, partly responsible for cancer relapse and metastasis. Research programs aimed at discovering anti-CSC agents have largely focused on biologics and purely organic molecules. Recently, we showed that a family of redox-active copper(II) complexes with phenanthroline-based ligands and nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin, are capable of potently and selectively killing breast CSCs. Herein we present analogous redox-inactive, zinc(II)-phenanthroline-indomethacin complexes with the ability to kill breast CSCs and bulk breast cancer cells with equal potency (in the submicro- or micromolar range). A single dose of the zinc(II) complexes could theoretically be administered to eliminate whole tumor populations. Excitingly, some of the zinc(II) complexes decrease the growth and viability of mammospheres to a comparable or higher degree than salinomycin, a compound known to effectively kill breast CSCs. As far as we are aware this is the first report to examine the anti-breast CSC activity of zinc(II)-containing compounds. View Full-Text
Keywords: metallopharmaceuticals; bioinorganic chemistry; zinc; nonsteroidal anti-inflammatory drug metallopharmaceuticals; bioinorganic chemistry; zinc; nonsteroidal anti-inflammatory drug
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MDPI and ACS Style

Rundstadler, T.K.; Eskandari, A.; Norman, S.M.; Suntharalingam, K. Polypyridyl Zinc(II)-Indomethacin Complexes with Potent Anti-Breast Cancer Stem Cell Activity. Molecules 2018, 23, 2253.

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