Regional Centre of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute (CATRIN), Palacký University, Šlechtitelů 241/27, CZ-783 71 Olomouc, Czech Republic.
Regional Centre of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute (CATRIN), Palacký University, Šlechtitelů 241/27, CZ-783 71 Olomouc, Czech Republic.
J Inorg Biochem. 2022 Jan;226:111639. doi: 10.1016/j.jinorgbio.2021.111639. Epub 2021 Oct 23.
Heteroleptic copper(II) complexes, containing prenylated flavonoid osajin isolated from the fruits of Maclura pomifera Schneid., were prepared and thoroughly characterized, including single crystal X-ray analysis. Some of the following complexes of the general composition [Cu(L)(bpy)]NO (1), [Cu(L)(dimebpy)]NO·2MeOH (2) [Cu(L)(phen)]NO·HO (3), [Cu(L)(bphen)]NO (4) and [Cu(L)(dppz)]NO (5), where HL stands for 3-(4-hydroxyphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-ene-1-yl)-4H,8H-benzo[1,2-b:3,4-b']dipyran-4-one (osajin), bpy = 2,2'-bipyridine, dimebpy = 4,4'-dimethyl-2,2'-bipyridine, phen = 1,10-phenanthroline, bphen = 4,7-diphenyl-1,10-phenanthroline and dppz = dipyrido[3,2-a:2',3'-c]phenazine, were also monitored for their solution stability and interactions with cysteine and glutathione by mass spectrometry. The in vitro cytotoxicity of the complexes was evaluated against a panel of eight human cancer cell lines: (MCF-7, HOS, A549, PC-3, A2780, A2780R, Caco-2, and THP-1). The results revealed high antiproliferative activity of the complexes with the best IC values of 0.5-3.4 μM for complexes (4) and (5), containing the bulkier N,N'-donor ligands (bphen, and dppz, respectively). The complexes also revealed a relatively low toxicity towards human hepatocytes (IC values are higher than 100 μM in some cases), and thus proved to be highly selective towards the cancer cells. On the other hand, the complexes showed a strong in vitro nuclease effect using the model pUC-19 plasmid. In the model of lipopolysaccharide-stimulated (LPS) THP-1 monocytes, the complexes revealed ability to lower the activity of nuclear factor kappa-B/activator protein 1 (NF-κB /AP-1) system and decrease the secretion of tumor necrosis factor alpha (TNF-α). Thus, the complexes have been identified as strong antiproliferative and anti-inflammatory compounds.
从枳实中分离得到的异戊烯基黄酮奥斯金的杂配铜（II）配合物被制备并进行了全面的表征，包括单晶 X 射线分析。以下是一些具有通式 [Cu(L)(bpy)]NO（1）、[Cu(L)(dimebpy)]NO·2MeOH（2）、[Cu(L)(phen)]NO·HO（3）、[Cu(L)(bphen)]NO（4）和[Cu(L)(dppz)]NO（5）的配合物，其中 HL 代表 3-(4-羟基苯基）-5-羟基-8,8-二甲基-6-(3-甲基-2-丁烯-1-基）-4H,8H-苯并[1,2-b:3,4-b']二吡喃-4-酮（奥斯金），bpy=2,2'-联吡啶，dimebpy=4,4'-二甲基-2,2'-联吡啶，phen=1,10-菲咯啉，bphen=4,7-二苯基-1,10-菲咯啉，dppz=二吡啶并[3,2-a:2',3'-c]吩嗪。这些配合物的溶液稳定性以及与半胱氨酸和谷胱甘肽的相互作用也通过质谱进行了监测。该配合物对 8 个人类癌细胞系（MCF-7、HOS、A549、PC-3、A2780、A2780R、Caco-2 和 THP-1）的体外细胞毒性进行了评估。结果表明，具有较大 N,N'-供体配体（bphen 和 dppz）的配合物（4）和（5）具有很高的抗增殖活性，IC 值为 0.5-3.4μM。该配合物对人肝细胞的毒性相对较低（在某些情况下，IC 值高于 100μM），因此对癌细胞具有高度选择性。另一方面，该配合物在模型 pUC-19 质粒中显示出很强的体外核酸酶活性。在脂多糖刺激（LPS）的 THP-1 单核细胞模型中，该配合物能够降低核因子 kappa-B/激活蛋白 1（NF-κB/AP-1）系统的活性并减少肿瘤坏死因子 alpha（TNF-α）的分泌。因此，这些配合物被鉴定为具有很强的抗增殖和抗炎作用的化合物。
