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

A series of sixteen ring-substituted N-arylcinnamanilides, previously described as highly antimicrobially effective against a wide spectrum of bacteria and fungi, together with two new derivatives from this group were prepared and characterized. Moreover, the molecular structure of (2E)-N-(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide as a model compound was determined using single-crystal X-ray analysis. All the compounds were tested for their anti-inflammatory potential, and most tested compounds significantly attenuated the lipopolysaccharide-induced NF-κB activation and were more potent than the parental cinnamic acid. (2E)-N-[2-Chloro-5-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide, (2E)-N-(2,6-dibromophenyl)- 3-phenylprop-2-enamide, and (2E)-N-(2,5-dichlorophenyl)-3-phenylprop-2-enamide demonstrated the highest inhibition effect on transcription factor NF-κB at the concentration of 2 µM and showed a similar effectiveness as the reference drug prednisone. Several compounds also decreased the level of TNF-α. Nevertheless, subsequent tests showed that the investigated compounds affect neither IκBα level nor MAPKs activity, which suggests that the N-arylcinnamanilides may have a different mode of action to prednisone. The modification of the C(2,5)' or C(2,6)' positions of the anilide core by rather lipophilic and bulky moieties seems to be preferable for the anti-inflammatory potential of these compounds.

• Klíčová slova
• X-ray structure, anti-inflammatory potential, cinnamamides, polypharmacology,
• MeSH
• antiflogistika chemická syntéza   chemie   farmakologie   MeSH
• cinnamáty chemická syntéza   chemie   farmakologie   MeSH
• krystalografie rentgenová MeSH
• lidé MeSH
• lipopolysacharidy škodlivé účinky   MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• NF-kappa B metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• THP-1 buňky MeSH
• TNF-alfa metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• cinnamáty MeSH
• lipopolysacharidy MeSH
• NF-kappa B MeSH
• TNF protein, human MeSH Prohlížeč
• TNF-alfa MeSH

We report in vitro and in vivo anti-inflammatory activities of a series of copper(II)-lawsone complexes of the general composition [Cu(Law)2(LN)x(H2O)(2-x)]·yH2O; where HLaw = 2-hydroxy-1,4-naphthoquinone, x = 1 when LN = pyridine (1) and 2-aminopyridine (3) and x = 2 when LN = imidazole (2), 3-aminopyridine (4), 4-aminopyridine (5), 3-hydroxypyridine (6), and 3,5-dimethylpyrazole (7). The compounds were thoroughly characterized by physical techniques, including single crystal X-ray analysis of complex 2. Some of the complexes showed the ability to suppress significantly the activation of nuclear factor κB (NF-κB) both by lipopolysaccharide (LPS) and TNF-alpha (complexes 3-7 at 100 nM level) in the similar manner as the reference drug prednisone (at 1 μM level). On the other hand, all the complexes 1-7 decreased significantly the levels of the secreted TNF-alpha after the LPS activation of THP-1 cells, thus showing the anti-inflammatory potential via both NF-κB moderation and by other mechanisms, such as influence on TNF-alpha transcription and/or translation and/or secretion. In addition, a strong intracellular pro-oxidative effect of all the complexes has been found at 100 nM dose in vitro. The ability to suppress the inflammatory response, caused by the subcutaneous application of λ-carrageenan, has been determined by in vivo testing in hind-paw edema model on rats. The most active complexes 1-3 (applied in a dose corresponding to 40 μmol Cu/kg), diminished the formation of edema simalarly as the reference drug indomethacine (applied in 10 mg/kg dose). The overall effect of the complexes, dominantly 1-3, shows similarity to anti-inflammatory drug benoxaprofen, known to induce intracellular pro-oxidative effects.

• MeSH
• antiflogistika terapeutické užití   MeSH
• edém farmakoterapie   MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
• krysa rodu Rattus MeSH
• krystalografie rentgenová MeSH
• lidé MeSH
• měď chemie   terapeutické užití   MeSH
• nádorové buněčné linie MeSH
• naftochinony chemie   terapeutické užití   MeSH
• NF-kappa B antagonisté a inhibitory   MeSH
• potkani Wistar MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zánět farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• lawsone MeSH Prohlížeč
• měď MeSH
• naftochinony MeSH
• NF-kappa B MeSH

Scorzonera species are used in different folk medicines to combat many diseases, including the illnesses connected with inflammation. Previous experiments showed anti-inflammatory activity of Scorzonera extracts in vivo. S. latifolia, S. cana var. jacquiniana, S. tomentosa, S. mollis ssp. szowitsii, S. eriophora, S. incisa, S. cinerea, and S. parviflora extracts were, therefore, evaluated for their inhibitory activities of TNF-α and IL-1β production, and NF-κB nuclear translocation in THP-1 macrophages. The HPLC analysis was carried out to elucidate and to compare the composition of these extracts. Major compounds of the tested extracts have been isolated using different chromatographic techniques and further tested for their inhibitory activities on TNF-α and IL-1β production. Several extracts showed promising anti-inflammatory activity in these in vitro tests. Results of HPLC analysis revealed chlorogenic acid as a compound present in all tested extracts. Hyperoside, quercetin-3-O-β-d-glucoside and rutin were also present in varying amount in some Scorzonera species analyzed. Furthermore, eight phenolics which were identified as quercetin-3-O-β-d-glucoside (1), hyperoside (2), hydrangenol-8-O-glucoside (3), swertisin (4), 7-methylisoorientin (5), 4,5-O-dicaffeoyl-quinic acid (6), 3,5-di-O-caffeoyl-quinic acid (7), and chlorogenic acid (8) have been isolated as major phenolic compounds of the tested extracts and, together with eight terpenoids (9-16) previously obtained from different Scorzonera species, have been tested for the inhibition of TNF-α production, unfortunately with no activity comparable with standard.

• Klíčová slova
• IL-1β, NF-κB, Scorzonera, TNF-α, anti-inflammatory activity, phenolic, triterpen,
• MeSH
• antiflogistika chemie   farmakologie   MeSH
• buněčné linie MeSH
• cytokiny metabolismus   MeSH
• fenoly chemie   farmakologie   MeSH
• lidé MeSH
• makrofágy účinky léků   imunologie   MeSH
• NF-kappa B metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• rostlinné extrakty analýza   farmakologie   MeSH
• Scorzonera chemie   MeSH
• signální transdukce účinky léků   MeSH
• techniky in vitro MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Turecko MeSH
• Názvy látek
• antiflogistika MeSH
• cytokiny MeSH
• fenoly MeSH
• NF-kappa B MeSH
• rostlinné extrakty MeSH

The gold(I) mixed-ligand complexes involving O-substituted derivatives of 9-deazahypoxanthine (HLn) and triphenylphosphine (PPh3) with the general formula [Au(Ln)(PPh3)] (1-5) were prepared and thoroughly characterized by elemental analysis, FT-IR and multinuclear NMR spectroscopy, ESI+ mass spectrometry, single crystal X-ray (HL5 and complex 2) and TG/DTA analyses. Complexes 1-5 were evaluated for their in vitro antitumor activity against nine human cancer lines, i.e. MCF7 (breast carcinoma), HOS (osteosarcoma), A549 (adenocarcinoma), G361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) and THP-1 (monocytic leukaemia), for their in vitro anti-inflammatory activity using a model of LPS-activated macrophages, and for their in vivo antiedematous activity by λ-carrageenan-induced hind paw edema model on rats. The results showed that the complexes 1-5 exhibit selective in vitro cytotoxicity against MCF7, HOS, 22Rv1, A2780 and A2780R, with submicromolar IC50 values for 2 against the MCF7 (0.6 µM) and HOS (0.9 µM). The results of in vitro cytotoxicity screening on primary culture of human hepatocytes (HEP220) revealed up to 30-times lower toxicity of compounds against healthy cells as compared with cancer cells. Additionally, the complexes 1-5 significantly influence the secretion and expression of pro-inflammatory cytokines TNF-α and IL-1β by a similar manner as a commercially used anti-arthritic drug Auranofin. The tested complexes also significantly influence the rate and overall volume of the edema, caused by the intraplantar application of λ-carrageenan polysaccharide to rats. Based on these promising results, the presented compounds could qualify to become feasible candidates for advanced testing as potential antitumor and anti-inflammatory drug-like compounds.

• MeSH
• antiflogistika chemie   farmakologie   terapeutické užití   MeSH
• edém farmakoterapie   MeSH
• hepatocyty účinky léků   MeSH
• hypoxanthiny chemie   farmakologie   terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   MeSH
• protinádorové látky chemie   farmakologie   terapeutické užití   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• zánět farmakoterapie   MeSH
• zlato chemie   farmakologie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 9-deazahypoxanthine MeSH Prohlížeč
• antiflogistika MeSH
• hypoxanthiny MeSH
• protinádorové látky MeSH
• zlato MeSH