title: Anticancer and Antibacterial Activity Studies of Gold(I)-Alkynyl Chromones.
abstract: Three gold(I) complexes of alkynyl chromones were synthesized and characterized. The single-crystal X-ray structure analysis of a dinuclear compound and of a flavone derivative exhibit a typical d10 gold(I)-alkynyl linear arrangement. All complexes were evaluated as anticancer and antibacterial agents against four human cancer cell lines and four pathogenic bacterial strains. All compounds show antiproliferative activity at lower micromolar range concentrations. Complex 4 showed a broad activity profile, being more active than the reference drug auranofin against HepG2, MCF-7 and CCRF-CEM cancer cells. The cellular uptake into MCF-7 cells of the investigated complexes was measured by atomic absorption spectroscopy (AAS). These measurements showed a positive correlation between an increased cellular gold content and the incubation time of the complexes. Unexpectedly an opposite effect was observed for the most active compound. Biological assays revealed various molecular mechanisms for these compounds, comprising: (i) thioredoxin reductase (TrxR) inhibition, (ii) caspases-9 and -3 activation; (iii) DNA damaging activity and (iv) cell cycle disturbance. The gold(I) complexes were also bactericidal against Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) bacterial strains, while showing no activity against the Gram-negative Escherichia coli bacterial strain.
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Łód´z, Pomorska 141/143, Łód´z PL-90236, Poland. pawelhikisz@gmail.com.
authors.forename: Paweł
authors.initials: P
authors.lastname: Hikisz
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, University of Łód´z, Tamka 12, Łód´z PL-91403, Poland. lukaszszczupak@interia.pl.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Szczupak
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Łód´z, Pomorska 141/143, Łód´z PL-90236, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Koceva-Chyła
authors.affiliation: Laboratory of Biologically Active Compounds, National Institute of Public Health-National Institute of Hygiene, Chocimska 24, Warsaw PL-00791, Poland. aguspiel@pzh.gov.pl.
authors.forename: Adam
authors.initials: A
authors.lastname: Gu Spiel
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstr. 55, Braunschweig D-38106, Germany. ingo.ott@tu-bs.de.
authors.forename: Luciano
authors.initials: L
authors.lastname: Oehninger
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstr. 55, Braunschweig D-38106, Germany. ingo.ott@tu-bs.de.
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
authors.affiliation: Institute of Chemistry, Faculty of Science, University of Neuchatel, Avenue de Bellevaux 51, Neuchatel CH-2000, Switzerland. Bruno.Therrien@unine.ch.
authors.forename: Bruno
authors.initials: B
authors.lastname: Therrien
authors.affiliation: Laboratory of Biologically Active Compounds, National Institute of Public Health-National Institute of Hygiene, Chocimska 24, Warsaw PL-00791, Poland. jsolecka@pzh.gov.pl.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Solecka
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, University of Łód´z, Tamka 12, Łód´z PL-91403, Poland. kondor15@wp.pl.
authors.forename: Konrad
authors.initials: K
authors.lastname: Kowalski
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006046:Gold / Q000737:chemistry; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D002867:Chromones; D006046:Gold; D020169:Caspases
keywords: TrxR; antibacterial activity; anticancer activity; caspases; ferrocene; gold(I) complexes