Anticancer and Antibacterial Activity Studies of Gold(I)-Alkynyl Chromones

Molecules

Paweł Hikisz²  Łukasz Szczupak³  Aneta Koceva-Chyła²  Adam Guśpiel¹  Luciano Oehninger⁵  Ingo Ott⁵  Bruno Therrien⁴  Jolanta Solecka¹  Konrad Kowalski³ 

[1] Laboratory of Biologically Active Compounds, National Institute of Public Health-National Institute of Hygiene, Chocimska 24, Warsaw PL-00791, Poland;Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, Łódź PL-90236, Poland;Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, Łódź PL-91403, Poland;Institute of Chemistry, Faculty of Science, University of Neuchatel, Avenue de Bellevaux 51, Neuchatel CH-2000, Switzerland;Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstr. 55, Braunschweig D-38106, Germany;

关键词: anticancer activity;    gold(I) complexes;    ferrocene;    TrxR;    caspases;    antibacterial activity;   

DOI  :  10.3390/molecules201119647

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.