INTRODUCTION: The MET inhibitor tepotinib demonstrated durable clinical activity in patients with advanced MET exon 14 (METex14) skipping NSCLC. We report detailed analyses of adverse events of clinical interest (AECIs) in VISION, including edema, a class effect of MET inhibitors. PATIENTS AND METHODS: Incidence, management, and time to first onset/resolution were analyzed for all-cause AECIs, according to composite categories (edema, hypoalbuminemia, creatinine increase, and ALT/AST increase) or individual preferred terms (pleural effusion, nausea, diarrhea, and vomiting), for patients with METex14 skipping NSCLC in the phase II VISION trial. RESULTS: Of 255 patients analyzed (median age: 72 years), edema, the most common AECI, was reported in 69.8% (grade 3, 9.4%; grade 4, 0%). Median time to first edema onset was 7.9 weeks (range: 0.1-58.3). Edema was manageable with supportive measures, dose reduction (18.8%), and/or treatment interruption (23.1%), and rarely prompted discontinuation (4.3%). Other AECIs were also manageable and predominantly mild/moderate: hypoalbuminemia, 23.9% (grade 3, 5.5%); pleural effusion, 13.3% (grade ≥ 3, 5.1%); creatinine increase, 25.9% (grade 3, 0.4%); nausea, 26.7% (grade 3, 0.8%), diarrhea, 26.3% (grade 3, 0.4%), vomiting 12.9% (grade 3, 1.2%), and ALT/AST increase, 12.2% (grade ≥ 3, 3.1%). GI AEs typically occurred early and resolved in the first weeks. CONCLUSION: Tepotinib was well tolerated in the largest trial of a MET inhibitor in METex14 skipping NSCLC. The most frequent AEs were largely mild/moderate and manageable with supportive measures and/or dose reduction/interruption, and caused few withdrawals in this elderly population.

• Klíčová slova
• Adverse event, Edema, MET inhibitor, Nausea, Non–small cell lung cancer,
• MeSH
• edém chemicky indukované   farmakoterapie   MeSH
• exony genetika   MeSH
• hypoalbuminemie farmakoterapie   MeSH
• inhibitory proteinkinas * škodlivé účinky   MeSH
• klinické zkoušky, fáze II jako téma MeSH
• kreatinin terapeutické užití   MeSH
• lidé MeSH
• mutace MeSH
• nádory plic * farmakoterapie   genetika   MeSH
• nauzea chemicky indukované   MeSH
• nemalobuněčný karcinom plic * farmakoterapie   genetika   MeSH
• piperidiny škodlivé účinky   MeSH
• pleurální výpotek MeSH
• průjem MeSH
• pyridaziny škodlivé účinky   MeSH
• pyrimidiny škodlivé účinky   MeSH
• senioři MeSH
• zvracení chemicky indukované   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inhibitory proteinkinas * MeSH
• kreatinin MeSH
• piperidiny MeSH
• pyridaziny MeSH
• pyrimidiny MeSH
• tepotinib MeSH Prohlížeč

We report an extensive structure-activity relationship optimization of polysubstituted pyrimidines that led to the discovery of 5-butyl-4-(4-benzyloxyphenyl)-6-phenylpyrimidin-2-amine, and its difluorinated analogue. These compounds are sub-micromolar inhibitors of PGE2 production (IC50 as low as 12 nM). In order to identify the molecular target of anti-inflammatory pyrimidines, we performed extensive studies including enzymatic assays, homology modeling and docking. The difluorinated analogue simultaneously inhibits two key enzymes of the arachidonic acid cascade, namely mPGES-1 and COX-2, with mPGES-1 inhibition being the principal mechanism of action. Other pyrimidines studied are potent mPGES-1 inhibitors with no observed inhibition of COX-1/2 enzymes. Moreover, the two most potent compounds proved to be significantly effective in vivo in a model of acute inflammation, suppressing carrageenan-induced rat paw edema by 36 and 46 %. The promising results of this study warrant further preclinical evaluation of selected anti-inflammatory candidates.

• Klíčová slova
• Suzuki Miyaura reaction, anti-inflammatory, mPGES-1, prostaglandin E2, pyrimidines,
• MeSH
• antiflogistika nesteroidní aplikace a dávkování   chemie   farmakologie   MeSH
• aplikace orální MeSH
• buněčné linie MeSH
• dinoproston antagonisté a inhibitory   biosyntéza   MeSH
• edém chemicky indukované   farmakoterapie   MeSH
• karagenan MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• molekulární struktura MeSH
• myši MeSH
• objevování léků MeSH
• pyrimidiny aplikace a dávkování   chemie   farmakologie   MeSH
• syntázy prostaglandinu E antagonisté a inhibitory   metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• dinoproston MeSH
• karagenan MeSH
• PTGES protein, human MeSH Prohlížeč
• Ptges protein, mouse MeSH Prohlížeč
• pyrimidiny MeSH
• syntázy prostaglandinu E MeSH

BACKGROUND: The frequency of allergic diseases is constantly rising. Dysregulated production of isotype E immunoglobulins is one of the key factors behind allergic reactions and its modulation is therefore an important target for pharmacological intervention. Natural products of the pseurotin family were reported to be inhibitors of IgE production in B-cells. Mechanistic details underlying these effects are however not well understood. PURPOSE: In the present study, we synthesized new analogs of natural pseurotins and extensively investigated their inhibitory effects on activation, proliferation and differentiation of B-cells, as well as on the production of IgE. STUDY DESIGN: Effects of two natural pseurotins (pseurotins A and D) and a collection of fully synthetic pseurotin analogs were studied on mouse B-cells stimulated by the combination of IL-4 and E. coli lipopolysaccharide. The IgE production was determined along with cell viability and cell proliferation. The phosphorylation of selected members of the STAT transcription factor family was subsequently investigated. Finally, the in vivo effect of pseurotin D on the ovalbumin-induced delayed type hypersensitivity response was tested in mice. RESULTS: We discovered that several fully synthetic pseurotin analogs were able to decrease the production of IgE in stimulated B-cells with potency comparable to that of pseurotins A and D. We found that the two natural pseurotins and the active synthetic analogs inhibited the phosphorylation of STAT3, STAT5 and STAT6 proteins in stimulated B-cells, resulting in the inhibition of B-cell proliferation and differentiation into the plasma cells. In vivo, pseurotin D decreased ovalbumin-induced foot pad edema. CONCLUSION: Our results advance the current mechanistic understanding of the pseurotin-induced inhibition of IgE production in B-cells by linking the effect to STAT signaling, and associated modulation of B-cell proliferation and differentiation. Together with our finding that structurally simpler pseurotin analogs were able to reproduce the effects of natural pseurotins, the presented work has implications for the future research on these secondary metabolites in the context of allergic diseases.

• Klíčová slova
• IgE, Immunoglobulins, Lymphocyte, Plasma cell, Pseurotins, STATs,
• MeSH
• aktivace lymfocytů účinky léků   MeSH
• B-lymfocyty cytologie   účinky léků   fyziologie   MeSH
• buněčná diferenciace účinky léků   MeSH
• edém chemicky indukované   farmakoterapie   MeSH
• Escherichia coli chemie   MeSH
• fosforylace účinky léků   MeSH
• imunoglobulin E krev   metabolismus   MeSH
• imunoglobulin M krev   metabolismus   MeSH
• lipopolysacharidy farmakologie   MeSH
• myši inbrední C57BL MeSH
• ovalbumin toxicita   MeSH
• plazmatické buňky cytologie   fyziologie   MeSH
• pyrrolidinony chemie   farmakologie   MeSH
• transkripční faktory STAT metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunoglobulin E MeSH
• imunoglobulin M MeSH
• lipopolysacharidy MeSH
• ovalbumin MeSH
• pseurotin d MeSH Prohlížeč
• pseurotin MeSH Prohlížeč
• pyrrolidinony MeSH
• transkripční faktory STAT MeSH

PURPOSE OF THE STUDY Bone marrow oedema (BMO) syndrome is a multifactorial condition. Various conservative treatment options include analgesic therapy, immobilisation of the affected joint and/or systemic intravenous iloprost therapy. Many studies have confirmed the positive effect of iloprost therapy, but only after short-term follow-up. The purpose of this study was to show that treatment with iloprost leads to positive long-term functional and radiological outcomes for BMO of the knee. MATERIAL AND METHODS Fifteen patients with BMO of the knee joint, ARCO stage 1-2, were included in this study. Various questionnaires, the Lysholm Score, the SF-36, WOMAC, Knee Society Score, and a visual analogue pain scale (VAS), were evaluated before and after iloprost therapy. All patients underwent MRI for radiological follow-up three months after treatment. RESULTS Significant improvements were found in the Lysholm Score, SF-36, WOMAC and KSS. In 80% of patients, follow-up MRI after three months showed complete regression of the oedema. Three patients received additional surgery after a follow-up period of 33 ± 7 months. CONCLUSIONS Based on the positive results of our study, we recommend treatment with iloprost for BMO of the knee in ARCO stage 1-2 patients. Key words:iloprost, bone marrow oedema, knee joint.

• MeSH
• edém * diagnóza   farmakoterapie   MeSH
• iloprost aplikace a dávkování   MeSH
• intravenózní podání MeSH
• kolenní kloub * diagnostické zobrazování   účinky léků   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• měření bolesti metody   MeSH
• monitorování léčiv metody   MeSH
• nemoci kostní dřeně * diagnóza   farmakoterapie   patofyziologie   MeSH
• rentgendiagnostika metody   MeSH
• vazodilatancia aplikace a dávkování   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Německo MeSH
• Názvy látek
• iloprost MeSH
• vazodilatancia 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

Soft glucocorticoids are compounds that are biotransformed to inactive and non-toxic metabolites and have fewer side effects than traditional glucocorticoids. A new class of 17β-carboxamide steroids has been recently introduced by our group. In this study, local anti-inflammatory activity of these derivatives was evaluated by use of the croton oil-induced ear edema test. Glucocorticoids with the highest maximal edema inhibition (MEI) were pointed out, and the systemic side effects of those with the lowest EC50 values were significantly lower in comparison to dexamethasone. A 3D-QSAR model was created and employed for the design of 27 compounds. By use of the sequential combination of ligand-based and structure-based virtual screening, three compounds were selected from the ChEMBL library and used as a starting point for the design of 15 derivatives. Molecular docking analysis of the designed derivatives with the highest predicted MEI and relative glucocorticoid receptor binding affinity (20, 22, 24-1, 25-1, 27, VS7, VS13, and VS14) confirmed the presence of interactions with the glucocorticoid receptor that are important for the activity.

• Klíčová slova
• Anti-inflammatory activity, QSAR, Rational drug design,
• MeSH
• antiflogistika škodlivé účinky   chemie   farmakologie   MeSH
• design s pomocí počítače * MeSH
• edém chemicky indukované   farmakoterapie   MeSH
• glukokortikoidy škodlivé účinky   chemie   farmakologie   MeSH
• krotonový olej MeSH
• krysa rodu Rattus MeSH
• kvantitativní vztahy mezi strukturou a aktivitou MeSH
• molekulární konformace MeSH
• nemoci ucha chemicky indukované   farmakoterapie   MeSH
• potkani Wistar MeSH
• racionální návrh léčiv MeSH
• simulace molekulového dockingu MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• glukokortikoidy MeSH
• krotonový olej MeSH

BACKGROUND: The aim of our experiments was to investigate the anti-inflammatory properties of casticin and chrysosplenol D, two flavonoids present in Artemisia annua L. METHODS: Topical inflammation was induced in ICR mice using croton oil. Mice were then treated with casticin or chrysosplenol D. Cutaneous histological changes and edema were assessed. ICR mice were intragastrically administrated with casticin or chrysosplenol D followed by intraperitoneal injection of lipopolysaccharide (LPS). Mouse Raw264.7 macrophage cells were incubated with casticin or chrysosplenol D. Intracellular phosphorylation was detected, and migration was assessed by trans-well assay. HT-29/NFκB-luc cells were incubated with casticin or chrysosplenol D in the presence or absence of LPS, and NF-κB activation was quantified. RESULTS: In mice, administration of casticin (0.5, 1 and 1.5μmol/cm(2)) and chrysosplenol D (1 and 1.5μmol/cm(2)) inhibited croton oil-induced ear edema (casticin: 29.39-64.95%; chrysosplenol D: 37.76-65.89%, all P<0.05) in a manner similar to indomethacin (0.5, 1 and 1.5μmol/cm(2); 55.63-84.58%). Casticin (0.07, 0.13 and 0.27mmol/kg) and chrysosplenol D (0.07, 0.14 and 0.28mmol/kg) protected against LPS-induced systemic inflammatory response syndrome (SIRS) in mice (all P<0.05), in a manner similar to dexamethasone (0.03mmol/kg). Casticin and chrysosplenol D suppressed LPS-induced release of IL-1 beta, IL-6 and MCP-1, inhibited cell migration, and reduced LPS-induced IκB and c-JUN phosphorylation in Raw264.7 cells. JNK inhibitor SP600125 blocked the inhibitory effect of chrysosplenol D on cytokine release. CONCLUSIONS: The flavonoids casticin and chrysosplenol D from A. annua L. inhibited inflammation in vitro and in vivo.

• Klíčová slova
• Artemisia annua L., Casticin, Chrysosplenol D, Flavonoids, Inflammation,
• MeSH
• Artemisia annua * MeSH
• buňky HT-29 MeSH
• dermatitida farmakoterapie   patologie   MeSH
• edém farmakoterapie   patologie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) MeSH
• flavonoidy izolace a purifikace   terapeutické užití   MeSH
• flavony izolace a purifikace   terapeutické užití   MeSH
• léky rostlinné čínské izolace a purifikace   terapeutické užití   MeSH
• lidé MeSH
• myši inbrední ICR MeSH
• myši MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zánět farmakoterapie   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• casticin MeSH Prohlížeč
• chrysosplenol D MeSH Prohlížeč
• flavonoidy MeSH
• flavony MeSH
• léky rostlinné čínské 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
• antitumorózní látky 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
• 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
• antitumorózní látky MeSH
• hypoxanthiny MeSH
• zlato MeSH

A series of gold(III) complexes involving differently substituted derivatives of a plant hormone N6-benzyladenine (HL1-5) is reported. The complexes have the general formula [Au(HL1-5)Cl3]∙nH2O (n=0 for 1, 3-5; and n=1 for 2), where N6-(2-fluorobenzyl)adenine (HL1), N6-(2-chlorobenzyl)adenine (HL2), N6-(3-chlorobenzyl)adenine (HL3), N6-(4-chlorobenzyl)adenine (HL4) and N6-(4-methylbenzyl)adenine (HL5) represent the N9-coordinated ligands. The results of thorough characterization (elemental and thermal analyses, FT-IR, Raman and NMR spectroscopies, ESI+ mass spectrometry, conductivity measurements, DFT calculations) showed that the presented complexes 1-5 involve a central gold(III) atom coordinated in a square-planar geometry by the N9 atom of the purine moiety of HL1-5 and by three chlorido ligands. The complexes (1-5) were studied in vitro for cytotoxicity and anti-inflammatory activity on LPS-activated macrophages (THP-1 cell line), and in vivo for anti-inflammatory effects (1, 2, 5) using the carrageenan-induced hind paw oedema model on rats. Surprisingly, the results on the in vitro level revealed that the complexes show negligible cytotoxicity and anti-inflammatory activity, however, the activity on the in vivo level was found to be significant, fully comparable with the utilized drug Indomethacin, or even better as compared to a gold-containing metallodrug Auranofin.

• Klíčová slova
• Adenine derivatives, Anti-inflammatory, Cytotoxicity, Gold(III) complexes, TNF-α,
• MeSH
• antiflogistika nesteroidní chemická syntéza   farmakologie   MeSH
• auranofin farmakologie   MeSH
• benzylové sloučeniny MeSH
• chloridy chemie   MeSH
• edém farmakoterapie   patologie   MeSH
• indomethacin farmakologie   MeSH
• kinetin chemie   MeSH
• komplexní sloučeniny chemická syntéza   farmakologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• ligandy MeSH
• monocyty cytologie   účinky léků   MeSH
• nádorové buněčné linie MeSH
• potkani Wistar MeSH
• puriny MeSH
• viabilita buněk účinky léků   MeSH
• zadní končetina MeSH
• zlato chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• auranofin MeSH
• benzylaminopurine MeSH Prohlížeč
• benzylové sloučeniny MeSH
• chloridy MeSH
• indomethacin MeSH
• kinetin MeSH
• komplexní sloučeniny MeSH
• ligandy MeSH
• puriny MeSH
• zlato MeSH

A series of gold(I) triphenylphosphine (PPh3) complexes (1-9) involving 2-chloro-N6-(substituted-benzyl)adenine derivatives as N-donor ligands was synthesized and thoroughly characterized by relevant methods, including electrospray-ionization (ESI) mass spectrometry and multinuclear NMR spectroscopy. The anti-inflammatory and antiedematous effects of three representatives 1, 5 and 9 were evaluated by means of in vitro model based on the expression of pro- and anti-inflammatory cytokines and influence of the complexes on selected forms of matrix metalloproteinases secreted by LPS-activated THP-1 monocytes and in vivo model evaluating the antiedematous effect of the complexes in the carrageenan-induced rat hind-paw edema model. In addition to the pharmacological observations, the affected hind paws were post mortem subjected to histological and immunohistochemical evaluations. The results of both in vivo and ex vivo methods revealed low antiedematous and anti-inflammatory effects of the complexes, even though the in vitro model identified them as promising anti-inflammatory acting compounds. The reason for this discrepancy lies probably in low stability of the studied complexes in biological environment, as demonstrated by the solution interaction studies with sulfur-containing biomolecules (cysteine and reduced glutathione) using the ESI mass spectrometry.

• MeSH
• adenin chemie   MeSH
• antiflogistika chemie   farmakologie   terapeutické užití   MeSH
• buněčné linie MeSH
• cytokiny metabolismus   MeSH
• edém farmakoterapie   MeSH
• ELISA MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
• krysa rodu Rattus MeSH
• ligandy MeSH
• organofosforové sloučeniny chemie   farmakologie   terapeutické užití   MeSH
• potkani Wistar MeSH
• techniky in vitro MeSH
• zlato chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenin MeSH
• antiflogistika MeSH
• cytokiny MeSH
• ligandy MeSH
• organofosforové sloučeniny MeSH
• triphenylphosphine MeSH Prohlížeč
• zlato MeSH