Hikisz Paweł, Szczupak Łukasz, Koceva-Chyła Aneta, Gu Spiel Adam, Oehninger Luciano, Ott Ingo, Therrien Bruno, Solecka Jolanta, Kowalski Konrad
Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Łód´z, Pomorska 141/143, Łód´z PL-90236, Poland.
Department of Organic Chemistry, Faculty of Chemistry, University of Łód´z, Tamka 12, Łód´z PL-91403, Poland.
Molecules. 2015 Oct 30;20(11):19699-718. doi: 10.3390/molecules201119647.
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.
合成并表征了三种炔基色酮的金（I）配合物。对一种双核化合物和一种黄酮衍生物进行的单晶X射线结构分析显示出典型的d10金（I）-炔基线性排列。评估了所有配合物对四种人类癌细胞系和四种致病细菌菌株的抗癌和抗菌活性。所有化合物在低微摩尔浓度范围内均显示出抗增殖活性。配合物4表现出广泛的活性谱，对HepG2、MCF-7和CCRF-CEM癌细胞的活性比参比药物金诺芬更高。通过原子吸收光谱法（AAS）测定了所研究配合物在MCF-7细胞中的细胞摄取情况。这些测量结果表明细胞内金含量的增加与配合物的孵育时间之间呈正相关。出乎意料的是，对活性最高的化合物观察到了相反的效果。生物学试验揭示了这些化合物的多种分子作用机制，包括：（i）抑制硫氧还蛋白还原酶（TrxR）；（ii）激活半胱天冬酶-9和-3；（iii）DNA损伤活性；以及（iv）细胞周期紊乱。金（I）配合物对革兰氏阳性的甲氧西林敏感金黄色葡萄球菌（MSSA）和耐甲氧西林金黄色葡萄球菌（MRSA）菌株也具有杀菌作用，而对革兰氏阴性的大肠杆菌菌株则无活性。
