Komplexy kovov s biologickou aktivitou predstavujú perspektívnu a rýchle sa rozvíjajúcu oblasť farmakoterapie. Po prvej časti prehľadu o metalofarmakách venovanej antimikróbnym účinkom komplexov kovov a ich využitiu v diagnostike ochorení a druhej časti zaoberajúcej sa úlohou týchto zlúčenín v liečbe rakoviny sa táto tretia a záverečná časť prehľadu zameriava na vybrané ďalšie aplikácie kovov v terapii (predovšetkým na terapiu reumatoidnej artritídy, niektorých psychických ochorení, diabetu, ako aj na chelatačnú terapiu). Popri stručnom náčrte historického vývoja klinického využitia danej kategórie liečiv sú diskutované tiež ich chemické vlastnosti, toxicita, klinické aplikácie a mechanizmus účinku. Tento stručný prehľad má za cieľ poskytnúť základnú orientáciu v tejto problematike pre farmaceutov, chemikov a ostatných záujemcov o danú oblasť z radov odbornej verejnosti, ako aj motivovať k ďalšiemu štúdiu tejto atraktívnej oblasti farmaceutického výskumu.
Bioactive metal complexes represent a promising and rapidly evolving area of pharmacotherapy. After the first part of our survey on metallopharmaceuticals dealing with antimicrobial activity of metal complexes and their application in diagnostics and the second part dedicated to anticancer properties of these compounds, this third and last part of the review focuses on several other applications of metals in therapy (mainly on the therapy of rheumatoid arthritis, some mental diseases, diabetes, as well as on chelation therapy). Following a brief account of the historical development of clinical use of the respective category of drugs, their chemical properties, toxicity, clinical applications and mechanism of action are discussed. The aim of this brief survey is to provide basic outline of the area of metallopharmacy, aimed at specialists in pharmacy and chemistry as well as at the general educated public.
- Klíčová slova
- metalofarmaka,
- MeSH
- chelátová terapie metody MeSH
- kovy * terapeutické užití MeSH
- lidé MeSH
- lithium terapeutické užití MeSH
- vanad terapeutické užití MeSH
- zlato terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Diabetes mellitus je chronické metabolické onemocnění projevující se hyperglykemií. V současnosti představuje ve světě jednu z nějčastějších zdravotních komplikací a jeho incidence stále stoupá. Hyperglykemie je způsobena sníženou či chybějící sekrecí inzulinu nebo rezistencí periferních tkání k jeho účinku. Nekompenzovaný diabetes a hyperglykemie přinášejí řadu dalších komplikací, jako je retinopatie, nefropatie, kardiovaskulární onemocnění a další. Prediabetes je stav, který často přechází v diabetes mellitus a projevuje se zvýšenou hladinou glukózy v krvi či narušenou glukózovou tolerancí.
Diabetes mellitus is a chronic metabolic disease which is characterized by hyperglycemia. Currently it is one of the major health problems in the world and its incidence is increasing. Hyperglycemia is caused either lowered or no insulin secretion or by peripheral tissues resistance to its effects. Uncompensated diabetes with inadequate regulation of the blood sugar imposes serious consequences for health, such as retinopathy, nephropathy, cardiovascular diseases, etc. Prediabetes is a stage which usually converts to diabetes mellitus, it´s characterized by above normal blood glucose levels or having impaired glucose tolerance. In prediabetes and type-2 diabetes mellitus, phytotherapy can be used in combination with a standard therapy (diet, peroral antidiabetics and insulin). There are many plants with antidiabetic effects and some of them were supported by clinical trials. This review presents four species of plants and mushrooms with antidiabetic effects: shaggy mane (Coprinus comatus), cinnamon (Cinnamomum spp.), guduchi (Tinospora cordata), and ginger (Zingiber officinale). They can be used as dietary supplements.
- Klíčová slova
- chebule srdčitá,
- MeSH
- Coprinus MeSH
- diabetes mellitus * farmakoterapie patofyziologie MeSH
- fytoterapie * MeSH
- houby MeSH
- krevní glukóza fyziologie účinky léků MeSH
- léčivé rostliny MeSH
- lidé MeSH
- prediabetes farmakoterapie patofyziologie MeSH
- skořicovník MeSH
- Tinospora MeSH
- vanad terapeutické užití MeSH
- zázvor lékařský MeSH
- Check Tag
- lidé MeSH
In this study, nanoparticle-incorporated nanofiber-covered yarns were prepared using a custom-made needle-free electrospinning system. The ultimate goal of this work was to prepare functional nanofibrous surfaces with antibacterial properties and realize high-speed production. As antibacterial agents, we used various amounts of copper oxide (CuO) and vanadium (V) oxide (V2O5) nanoparticles (NPs). Three yarn preparation speeds (100 m/min, 150 m/min, and 200 m/min) were used for the nanofiber-covered yarn. The results indicate a relationship between the yarn speed, quantity of NPs, and antibacterial efficiency of the material. We found a higher yarn speed to be associated with a lower reduction in bacteria. NP-loaded nanofiber yarns were proven to have excellent antibacterial properties against Gram-negative Escherichia coli (E. coli). CuO exhibited a greater inhibition and bactericidal effect against E. coli than V2O5. In brief, the studied samples are good candidates for use in antibacterial textile surface applications, such as wastewater filtration. As greater attention is being drawn to this field, this work provides new insights regarding the antibacterial textile surfaces of nanofiber-covered yarns.
- MeSH
- antibakteriální látky chemie MeSH
- měď chemie MeSH
- nanovlákna chemie MeSH
- polyvinyly chemie MeSH
- vanad chemie MeSH
- Publikační typ
- časopisecké články MeSH
Ten new vanadocene complexes bearing N,N'-chelating ligands were prepared, characterized, and their cytotoxicity toward a panel of cancer cells was measured. Structures of four vanadocene compounds were determined by single crystal X-ray diffraction analysis. Complexes containing 1,2-bis(phenylimino)acenaphthene (bian) and 1,2-bis(4-methoxyphenylimino)acenaphthene (4-MeO-bian) exhibit higher cytotoxicity than those with dipyrido[3,2-a:2',3'-c]phenazine (dppz) and (E)-N-((pyridin-2-yl)methylene)benzenamine (pyma). In light of the finding, cytotoxic mechanisms of two highly effective complexes [(η5-C5H4Me)2V(bian)][OTf]2 (3b) and [(η5-C5H4Me)2V(4-MeO-bian)][OTf]2 (4b) against human A549 lung adenocarcinoma cells were investigated by following membrane leakage of intracellular lactate dehydrogenase, Trypan Blue staining and activation of tumor protein p53 (p53). Evaluated complexes have a potent dose-dependent antiproliferative activity, causing cell cycle redistribution by the increased accumulation of cells in the G2 and S phase. In accord with the observed cell cycle deceleration, cyclin-dependent kinase inhibitor-interacting protein 1 (p21WAF1/Cip1), extracellular signal-regulated kinases 1 and 2 (ERK1/2), Checkpoint kinase 1 (Chk1), Checkpoint kinase 2 (Chk2) and their phosphorylated forms Chk1 at serine 345 and Chk2 at threonine 68 increased. In the cells exposed to complexes, dose- and time-dependent apoptotic process is initiated by the activation of the initiator caspase 8, followed by activation of effector caspase 3/7 and phosphatidylserine externalization. Moreover, because of treatment, A549 cells activate prosurvival mitogen-activated protein kinases (MAPK) signaling and up-regulate antiapoptotic protein B-cell lymphoma (Bcl-2), thereby promoting evasion of cell death. Both complexes exhibited considerably higher cytotoxic effect than the reference anticancer drug cis-platin and the cytotoxicity was more pronounced at higher treatment time.
- MeSH
- apoptóza účinky léků MeSH
- chelátory chemická syntéza chemie farmakologie MeSH
- kaspasy metabolismus MeSH
- komplexní sloučeniny chemická syntéza chemie farmakologie MeSH
- kontrolní body fáze G2 buněčného cyklu účinky léků MeSH
- lidé MeSH
- ligandy MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- vanad chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
KEY MESSAGE: Vanadium compounds increased the content and release of distinct isoflavones in a Trifolium pratense suspension culture. Regarding transport-mechanism inhibitors, the process was mostly facilitated by ABC proteins and vesicular transport. The transport of isoflavones and other secondary metabolites is an important part of metabolism within plants and cultures in vitro regarding their role in defence against various abiotic and biotic stressors. This research focuses on the way how to increase production and exudation of isoflavones by application of chemical elicitor and the basic identification of their transport mechanisms across cell membranes. The release of five isoflavones (genistin, genistein, biochanin A, daidzein, and formononetin) into a nutrient medium was determined in a Trifolium pratense var. DO-8 suspension culture after two vanadium compound treatments and cultivation for 24 and 48 h. The NH4VO3 solution caused a higher concentration of isoflavones in the medium after 24 h. This increased content of secondary metabolites was subsequently suppressed by distinct transport-mechanism inhibitors. The transport of isoflavones in T. pratense was mostly affected by ABC inhibitors from the multidrug-resistance-associated protein subfamily, but the genistein concentration in the medium was lower after treatment with multidrug-resistance protein subfamily inhibitors. Brefeldin A, which blocks vesicular transport, also decreased the concentration of some isoflavones in the nutrient medium.
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- Klíčová slova
- muscazone, stizolobic acid,
- MeSH
- Amanita * chemie patogenita MeSH
- aminokyseliny dikarboxylové MeSH
- betalainy MeSH
- biologické toxiny MeSH
- halucinace chemicky indukované MeSH
- isoxazoly MeSH
- kyselina ibotenová MeSH
- lidé MeSH
- muscimol MeSH
- muskarin MeSH
- otrava houbami patofyziologie MeSH
- oxazoly MeSH
- polysacharidy MeSH
- vanad MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
This work describes cytotoxic effect of non-platinum metal-based compounds on the human T-leukemic cells with different p53 status (p53 wild-type MOLT-4 and p53-deficient Jurkat cells). The cytotoxic and apoptosis-inducing effect of the vanadium complex [(η(5)-C5H5)2V(5-NH2-phen)]OTf (V1) and molybdenum complex [(η(3)-C3H5)Mo(CO)2(phen)Cl] (Mo1) were studied using flow cytometry, spectrophotometry and Western blotting. We found that the cytotoxic effect of both tested complexes after 24 h is higher against the both examined cell lines than that of cis-platin (cis-DDP). At later investigated time intervals of 48 and 72 h, the cytotoxic effect of the cis-DDP increased but the values of the cytotoxicity of the tested V1 and Mo1 complexes remained unchanged, with the cytotoxicity of V1 comparable to that of cis-DDP. Furthermore we observed that the apoptotic process was induced by the activation of the caspases 9 (intrinsic pathway) and 8 (extrinsic pathway) in cells exposed to evaluated complexes. In case of the p53 wild-type MOLT-4 cells, the expression of the tumor-suppressor protein p53 and its form phosphorylated at the serine 15 increased after both V1 and Mo1 treatment, similar to the effect of cis-DDP.
- MeSH
- apoptóza účinky léků MeSH
- fosforylace účinky léků MeSH
- kaspasy metabolismus MeSH
- leukemie T-buněčná farmakoterapie metabolismus patologie MeSH
- lidé MeSH
- molybden chemie farmakologie MeSH
- nádorové buněčné linie MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- organokovové sloučeniny chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- serin metabolismus MeSH
- vanad chemie farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The structures of two stereoisomers of the chiral anion [VO2(N-salicylidene-isoleucinato)](-) possessing three centers of chirality, the vanadium atom (configuration A/C) and the isoleucine moiety (configuration R/S on alpha and beta carbons), are presented. The absolute configuration of all available stereosiomers, CSS, ARR, CSR and ARS, was determined by electronic circular dichroism (ECD), which allows distinguishing between diastereomers, and by vibrational circular dichroism (VCD) capable of differentiating between all four stereoisomers. The comparison of experimental VCD and infrared (IR) spectra with simulated spectra for band assignment revealed the IR spectra of the diastereomers differing significantly in the CH stretching region of the aromatic part in the molecule. Crystallization from binary systems composed of equal ratio of two stereoisomers of isoleucine, unveiled the lower solubility of CSS and ARR stereoisomers, while a longer crystallization time of the CSR and ARS stereoisomers allowed proceeding the vanadium-catalyzed epimerization, leading to the subsequent presence of the CSS and ARR stereoisomers in the product obtained.
- MeSH
- isomerie MeSH
- komplexní sloučeniny chemie MeSH
- Schiffovy báze chemie MeSH
- vanad chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- biomedicínský výzkum * trendy MeSH
- diabetes mellitus 2. typu etiologie farmakoterapie MeSH
- farmakoterapie MeSH
- flavonoidy terapeutické užití MeSH
- inkretiny * terapeutické užití MeSH
- inzulin lidský analogy a deriváty terapeutické užití MeSH
- inzulin * analogy a deriváty nedostatek terapeutické užití MeSH
- inzulinová rezistence MeSH
- lidé MeSH
- peptidy terapeutické užití MeSH
- selen terapeutické užití MeSH
- sulfonylmočovinové sloučeniny metabolismus terapeutické užití MeSH
- vanad terapeutické užití MeSH
- Check Tag
- lidé MeSH
Ti-6Al-4V hour-glass shaped rotating beam specimens with duplex microstructure were processed by electric discharge machining (EDM). A comparatively high peak current of 29A was utilized in order to increase surface roughness for improved osteointegration. High cycle fatigue (HCF) tests were performed in rotating beam loading (R=-1) on these EDM specimens and results were compared with electrolytically polished specimens serving as reference. As expected, the HCF performance of EDM specimens was inferior to the electrolytically polished specimens. A detailed study of fatigue crack nucleation and microcrack growth was carried out on failed specimens by SEM. The poor HCF strength of EDM specimens is explained by early crack nucleation due to the high notch sensitivity of Ti-6Al-4V. In addition, process-induced residual tensile stresses and microstructural effects may also account for the drastic loss in HCF performance relative to the electropolished baseline.
- MeSH
- elektrická impedance MeSH
- elektřina MeSH
- elektrody MeSH
- hliník chemie MeSH
- kosti a kostní tkáň cytologie MeSH
- mechanické jevy MeSH
- povrchové vlastnosti MeSH
- proliferace buněk MeSH
- protézy a implantáty MeSH
- slitiny chemie MeSH
- teplota MeSH
- titan chemie MeSH
- vanad chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
