A series of new heteroleptic copper(II) complexes of the composition [Cu(L)(bpy)]NO3·2MeOH (1), [Cu(L)(dimebpy)]NO3·2H2O (2), [Cu(L)(phen)]NO3·2MeOH (3), [Cu(L)(bphen)]NO3·MeOH (4), [Cu(L)(dppz)]NO3·MeOH (5) was prepared, where HL = 3-(3,4-dihydroxyphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-ene-1-yl)-4H,8H-benzo[1,2-b:3,4-b']dipyran-4-one, (pomiferin) and 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. The complexes were characterized using elemental analysis, infrared and UV/Vis spectroscopies, mass spectrometry, thermal analysis and conductivity measurements. The in vitro cytotoxicity, screened against eight human cancer cell lines (breast adenocarcinoma (MCF-7), osteosarcoma (HOS), lung adenocarcinoma (A549), prostate adenocarcinoma (PC-3), ovarian carcinoma (A2780), cisplatin-resistant ovarian carcinoma (A2780R), colorectal adenocarcinoma (Caco-2) and monocytic leukemia (THP-1), revealed the complexes as effective antiproliferative agents, with the IC50 values of 2.2-13.0 μM for the best performing complexes 3 and 5. All the complexes 1-5 showed the best activity against the A2780R cells (IC50 = 2.2-6.6 μM), and moreover, the complexes demonstrated relatively low toxicity on healthy human hepatocytes, with IC50 > 100 μM. The complexes were evaluated by the Annexin V/propidium iodide apoptosis assay, induction of cell cycle modifications in A2780 cells, production of reactive oxygen species (ROS), perturbation of mitochondrial membrane potential, inhibition of apoptosis and inflammation-related signaling pathways (NF-κB/AP-1 activity, NF-κB translocation, TNF-α secretion), and tested for nuclease mimicking activity. The obtained results revealed the corresponding complexes to be effective antiproliferative and anti-inflammatory agents.

• Klíčová slova
• ROS, cell cycle, copper(II) complexes, in vitro cytotoxicity, inflammation, nuclease activity, pomiferin,
• MeSH
• antiflogistika farmakologie   MeSH
• apoptóza účinky léků   MeSH
• benzopyrany chemie   farmakologie   MeSH
• flavonoidy metabolismus   farmakologie   MeSH
• isoflavony chemie   farmakologie   MeSH
• komplexní sloučeniny chemie   farmakologie   MeSH
• lidé MeSH
• měď chemie   metabolismus   farmakologie   MeSH
• nádorové buněčné linie MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky farmakologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• benzopyrany MeSH
• flavonoidy MeSH
• isoflavony MeSH
• komplexní sloučeniny MeSH
• měď MeSH
• pomiferin MeSH Prohlížeč
• protinádorové látky MeSH
• reaktivní formy kyslíku MeSH

Background: Oxidative stress is a key factor in the pathophysiology of many diseases. This study aimed to verify the antioxidant activity of selected plant phenolics in cell-based assays and determine their direct or indirect effects. Methods: The cellular antioxidant assay (CAA) assay was employed for direct scavenging assays. In the indirect approach, the influence of each test substance on the gene and protein expression and activity of selected antioxidant enzymes was observed. One assay also dealt with activation of the Nrf2-ARE pathway. The overall effect of each compound was measured using a glucose oxidative stress protection assay. Results: Among the test compounds, acteoside showed the highest direct scavenging activity and no effect on the expression of antioxidant enzymes. It increased only the activity of catalase. Diplacone was less active in direct antioxidant assays but positively affected enzyme expression and catalase activity. Morusin showed no antioxidant activity in the CAA assay. Similarly, pomiferin had only mild antioxidant activity and proved rather cytotoxic. Conclusions: Of the four selected phenolics, only acteoside and diplacone demonstrated antioxidant effects in cell-based assays.

• Klíčová slova
• CAA, Nrf2-ARE, antioxidants, catalase, glucose toxicity, plant phenolics, superoxide dismutase,
• MeSH
• antioxidační responzivní elementy MeSH
• antioxidancia chemie   farmakologie   MeSH
• biologické markery MeSH
• exprese genu MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• fenoly chemie   farmakologie   MeSH
• glukosa MeSH
• lidé MeSH
• molekulární struktura MeSH
• oxidační stres MeSH
• protinádorové látky chemie   farmakologie   MeSH
• rostlinné extrakty chemie   farmakologie   MeSH
• superoxiddismutasa 1 genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• biologické markery MeSH
• faktor 2 související s NF-E2 MeSH
• fenoly MeSH
• glukosa MeSH
• NFE2L2 protein, human MeSH Prohlížeč
• protinádorové látky MeSH
• rostlinné extrakty MeSH
• SOD1 protein, human MeSH Prohlížeč
• superoxiddismutasa 1 MeSH