Ferrocenyl and dicobalt hexacarbonyl chromones--new organometallics inducing oxidative stress and arresting human cancer cells in G2/M phase

Konrad Kowalski; Paweł Hikisz; Łukasz Szczupak; Bruno Therrien; Aneta Koceva-Chyła

doi:10.1016/j.ejmech.2014.05.023

Ferrocenyl and dicobalt hexacarbonyl chromones--new organometallics inducing oxidative stress and arresting human cancer cells in G2/M phase

Eur J Med Chem. 2014 Jun 23:81:289-300. doi: 10.1016/j.ejmech.2014.05.023. Epub 2014 May 9.

Authors

Konrad Kowalski¹, Paweł Hikisz², Łukasz Szczupak³, Bruno Therrien⁴, Aneta Koceva-Chyła²

Affiliations

¹ Faculty of Chemistry, Department of Organic Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland. Electronic address: konkow@chemia.uni.lodz.pl.
² Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236, Łódź, Poland.
³ Faculty of Chemistry, Department of Organic Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland.
⁴ Institute of Chemistry, University of Neuchatel, Avenue de Bellevaux 51, CH-2000 Neuchatel, Switzerland.

PMID: 24852276
DOI: 10.1016/j.ejmech.2014.05.023

Abstract

The straightforward syntheses of four new ferrocenyl and dicobalt hexacarbonyl chromones are presented. The redox behavior of the novel metallo-chromones has been examined by cyclic voltammetry (CV), revealing a reversible behavior of the ferrocenyl groups, while the dicobalt hexacarbonyl derivatives show irreversible oxidation. The anticancer activity of the products has been evaluated against hepatocellular carcinoma (Hep G2), ER+ (MCF-7) and ER- (MDA-MB-231) breast adenocarcinoma, and leukemic (CCRF-CEM) human cancer cell lines. The mechanism of action for the most active complexes has been investigated and it seems to involve oxidative stress and apoptosis induction. Moreover, the results show that the investigated metallo-chromones generate damage to DNA and arrest the cell cycle in G2/M phase.

Keywords: Anticancer activity; Apoptosis; Cell cycle; Chromone; Ferrocene; ROS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Cycle Checkpoints / drug effects*
Cell Division / drug effects*
Cell Proliferation / drug effects
Cell Survival / drug effects
Chromones / chemistry*
Cobalt / chemistry*
DNA / chemistry
DNA / metabolism
DNA Damage
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Ferrous Compounds / chemistry*
G2 Phase / drug effects*
Hep G2 Cells
Humans
MCF-7 Cells
Molecular Structure
Organometallic Compounds / chemical synthesis
Organometallic Compounds / chemistry
Organometallic Compounds / pharmacology*
Oxidative Stress / drug effects*
Reactive Oxygen Species / metabolism
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Chromones
Ferrous Compounds
Organometallic Compounds
Reactive Oxygen Species
Cobalt
DNA