Heteroleptic copper(II) complexes of prenylated flavonoid osajin behave as selective and effective antiproliferative and anti-inflammatory agents
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
34717252
DOI
10.1016/j.jinorgbio.2021.111639
PII: S0162-0134(21)00286-5
Knihovny.cz E-zdroje
- Klíčová slova
- Cell viability, Copper(II) complexes, In vitro cytotoxicity, Inflammation, Osajin, X-ray structure,
- MeSH
- antiflogistika * chemie farmakologie MeSH
- buňky A549 MeSH
- buňky PC-3 MeSH
- Caco-2 buňky MeSH
- hepatocyty metabolismus MeSH
- isoflavony * chemie farmakologie MeSH
- komplexní sloučeniny * chemie farmakologie MeSH
- lidé MeSH
- měď * chemie farmakologie MeSH
- MFC-7 buňky MeSH
- proliferace buněk účinky léků MeSH
- THP-1 buňky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiflogistika * MeSH
- isoflavony * MeSH
- komplexní sloučeniny * MeSH
- měď * MeSH
- osajin MeSH Prohlížeč
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)]NO3 (1), [Cu(L)(dimebpy)]NO3·2MeOH (2) [Cu(L)(phen)]NO3·H2O (3), [Cu(L)(bphen)]NO3 (4) and [Cu(L)(dppz)]NO3 (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 IC50 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 (IC50 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.
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