Copper(II) Complexes Containing Natural Flavonoid Pomiferin Show Considerable In Vitro Cytotoxicity and Anti-inflammatory Effects
A series of new heteroleptic copper(II) complexes of the composition [Cu(L)(bpy)]NO<sub>3</sub>·2MeOH (<b>1</b>), [Cu(L)(dimebpy)]NO<sub>3</sub>·2H<sub>2</sub>O (<b>2</b>), [Cu(L)(phen)]NO<sub>3</sub>·2MeOH (<b>3</b>...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/14/7626 |
| Summary: | A series of new heteroleptic copper(II) complexes of the composition [Cu(L)(bpy)]NO<sub>3</sub>·2MeOH (<b>1</b>), [Cu(L)(dimebpy)]NO<sub>3</sub>·2H<sub>2</sub>O (<b>2</b>), [Cu(L)(phen)]NO<sub>3</sub>·2MeOH (<b>3</b>), [Cu(L)(bphen)]NO<sub>3</sub>·MeOH (<b>4</b>), [Cu(L)(dppz)]NO<sub>3</sub>·MeOH (<b>5</b>) was prepared, where HL = 3-(3,4-dihydroxyphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-ene-1-yl)-4<i>H</i>,8<i>H</i>-benzo[1,2-<i>b</i>:3,4-<i>b</i>′]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-<i>a</i>:2′,3′-<i>c</i>]phenazine. The complexes were characterized using elemental analysis, infrared and U<i>V/V</i>is 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 IC<sub>50</sub> 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 (IC<sub>50</sub> = 2.2–6.6 μM), and moreover, the complexes demonstrated relatively low toxicity on healthy human hepatocytes, with IC<sub>50</sub> > 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. |
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| ISSN: | 1661-6596 1422-0067 |