Ferrocenyl and dicobalt hexacarbonyl chromones--new organometallics inducing oxidative stress and arresting human cancer cells in G2/M phase.
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.
Faculty of Chemistry, Department of Organic Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland. Electronic address: konkow@chemia.uni.lodz.pl.
Konrad
K
Kowalski
Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236, Łódź, Poland.
Paweł
P
Hikisz
Faculty of Chemistry, Department of Organic Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland.
Łukasz
Ł
Szczupak
Institute of Chemistry, University of Neuchatel, Avenue de Bellevaux 51, CH-2000 Neuchatel, Switzerland.
Bruno
B
Therrien
Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236, Łódź, Poland.
Aneta
A
Koceva-Chyła
D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000737:chemistry*; D003035:Cobalt / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005296:Ferrous Compounds / Q000737:chemistry*; D016195:G2 Phase / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D002867:Chromones; D005296:Ferrous Compounds; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D003035:Cobalt; D004247:DNA
Anticancer activity; Apoptosis; Cell cycle; Chromone; Ferrocene; ROS