The current epidemic of antibiotic-resistant infections urges to develop alternatives to less-effective antibiotics. To assess anti-bacterial potential, a novel coordinate compound (RU-S4) was synthesized using ruthenium-Schiff base-benzimidazole ligand, where ruthenium chloride was used as the central atom. RU-S4 was characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), and Raman spectroscopy. Antibacterial effect of RU-S4 was studied against Staphylococcus aureus (NCTC 8511), vancomycin-resistant Staphylococcus aureus (VRSA) (CCM 1767), methicillin-resistant Staphylococcus aureus (MRSA) (ST239: SCCmecIIIA), and hospital isolate Staphylococcus epidermidis. The antibacterial activity of RU-S4 was checked by growth curve analysis and the outcome was supported by optical microscopy imaging and fluorescence LIVE/DEAD cell imaging. In vivo (balb/c mice) infection model prepared with VRSA (CCM 1767) and treated with RU-S4. In our experimental conditions, all infected mice were cured. The interaction of coordination compound with bacterial cells were further confirmed by cryo-scanning electron microscope (Cryo-SEM). RU-S4 was completely non-toxic against mammalian cells and in mice and subsequently treated with synthesized RU-S4.

• MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• Bacteria účinky léků   MeSH
• buněčné linie MeSH
• komplexní sloučeniny chemie   farmakologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• molekulární struktura MeSH
• myši MeSH
• Ramanova spektroskopie MeSH
• ruthenium chemie   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

In the present study, two binuclear copper(II) coordination compounds bridged by hydroxy- and thiodipropionic acid have been synthesized. The structure of compounds was determined by X-ray crystallography. The central copper atoms exist in square pyramidal surroundings. Basal plane is formed by nitrogen atoms of amines and oxygen atoms of bridges, whereas apical positions are occupied by oxygen atoms of coordinated water molecules. Temperature dependence study of magnetic susceptibility proved strong antiferromagnetic exchange between copper atoms in hydroxy-bridged complex. These coordination compounds were also tested for their biological activities in vitro. Both coordination compounds exhibit pronounced cytocompatibility in mammalian epithelial cells with no induction of oxidative stress and DNA fragmentation. Moreover, synthesized compounds are hemocompatible and do not alter expression of a marker of multiple cellular stress, p53. On the other hand, both compounds had stimulatory effect on expression of metallothioneins (MT-1/2 and MT-3). Antimicrobial testing on Escherichia coli, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus revealed that both copper compounds exhibit antibacterial activity regardless the cell wall composition. Overall, current work presents a synthesis of Cu(II) coordination compounds with interesting biological behavior and with a promising potential to be further tested in pre-clinical models.

• MeSH
• antibakteriální látky chemická syntéza   chemie   farmakologie   MeSH
• biokompatibilní materiály MeSH
• hemolýza účinky léků   MeSH
• hojení ran účinky léků   MeSH
• komplexní sloučeniny chemická syntéza   chemie   MeSH
• lidé MeSH
• měď chemie   MeSH
• methicilin rezistentní Staphylococcus aureus účinky léků   MeSH
• mikrobiální testy citlivosti MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• propionáty chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

A new thiourea ligand (HL), namely N-(4-chlorophenyl)morpholine-4-carbothioamide and its Co(III), Ni(II) and Ag(I) complexes (1a, 1b and 1c) were synthesized and investigated by Fourier-transform infrared, 1H NMR and UV-visible spectroscopies. The compounds HL and 1c were characterized by single-crystal X-ray crystallography revealing the triclinic space group P[Formula: see text] for both compounds. The inhibitory effect of HL ligand, 1a, 1b, and 1c complexes was investigated with in vitro tests on Gram-positive and Gram-negative bacteria. For the 1c complex, the results showed that the coordination of the HL to Ag(I) ion increased its antibacterial effect especially against E. coli. The assays also indicated that for the same bacteria strains, the new complexes showed higher activity than the ligand, with the relative activity 1c > 1b > 1a > HL. Moreover, all samples were more suitable antimicrobial agents against the Gram-negative than those of the Gram-positive bacteria. Eventually, the relationship between the structure and bactericidal activities of these specimens was examined by calculating frontier molecular orbital (HOMO and LUMO) energies using density functional theory method at the 6-31 G*/LANL2DZ level of theory.

• MeSH
• antibakteriální látky chemická syntéza   chemie   farmakologie   MeSH
• gramnegativní bakterie účinky léků   MeSH
• grampozitivní bakterie účinky léků   MeSH
• komplexní sloučeniny chemická syntéza   chemie   farmakologie   MeSH
• krystalografie rentgenová MeSH
• magnetická rezonanční spektroskopie MeSH
• mikrobiální testy citlivosti MeSH
• molekulární struktura MeSH
• morfoliny chemická syntéza   chemie   farmakologie   MeSH
• spektrofotometrie ultrafialová MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• thioamidy chemická syntéza   chemie   farmakologie   MeSH
• thiomočovina metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• chelátory chemická syntéza   MeSH
• heterocyklické sloučeniny analogy a deriváty   chemická syntéza   MeSH

• MeSH
• adjuvantní chemoterapie MeSH
• klinické lékařství MeSH
• nádory terapie   MeSH
• preklinické hodnocení léčiv MeSH
• sloučeniny platiny terapeutické užití   MeSH
• Publikační typ
• souborné dílo MeSH

• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• onkologie
• farmacie a farmakologie
• farmakoterapie

Metal-based coordination compounds have been used throughout the history of human medicine to treat various diseases, including cancer. Since the discovery of cisplatin in 1965, a great number of metal coordination complexes, such as platinum, ruthenium, gold or copper have been designed, synthesized and tested in order to develop clinically effective and safe drugs. Currently, many reviews cover applications of cytostatic metal complexes pointing out the most promising examples of platinum- and non-platinum-based compounds in preclinical and clinical trials. However, recent comprehensive reviews covering chemical and biological aspects of metal-based coordination compounds in cancer therapy are still rare. In this review we wish to provide an overview of the coordination chemistry of current and novel cytostatic compounds, including an outline of their design and rationale of synthesis, and summarize bio-chemical reactivity and physicochemical properties of candidate metal complexes.

• MeSH
• cisplatina dějiny   farmakologie   terapeutické užití   MeSH
• galium dějiny   farmakologie   terapeutické užití   MeSH
• genomika metody   trendy   MeSH
• individualizovaná medicína metody   trendy   využití   MeSH
• kobalt dějiny   farmakologie   terapeutické užití   MeSH
• komplexní sloučeniny * farmakologie   terapeutické užití   MeSH
• lidé MeSH
• měď farmakologie   terapeutické užití   MeSH
• metabolomika metody   trendy   MeSH
• mezioborová komunikace MeSH
• proteomika metody   trendy   MeSH
• protinádorové látky * farmakologie   terapeutické užití   MeSH
• sloučeniny ruthenia dějiny   farmakologie   terapeutické užití   MeSH
• sloučeniny železa dějiny   farmakologie   terapeutické užití   MeSH
• sloučeniny zlata dějiny   farmakologie   terapeutické užití   MeSH
• statistika jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

By means of selective deuterium labeling of 1-aza[6]helicene combined with resolution of the enantiomers, chiral discrimination in silver(I)-bound dimers of the type [LAgL']+ is probed by electrospray mass spectrometry. The analysis of the results reveals a pronounced preference for the formation of homochiral dimers (P,P and M,M, respectively) over the statistically preferred heterochiral variant (P,M), which is fully consistent with previous data about the formation of homochiral dimers in the condensed phase. Further, competitive experiments with mixtures of 1- and 2-aza[6]helicene suggest a largely preferred coordination of 1-aza[6]helicene to the silver(I) cation.

• MeSH
• azosloučeniny MeSH
• financování organizované MeSH
• isomerie MeSH
• ligandy MeSH
• organokovové sloučeniny chemie   MeSH
• polycyklické sloučeniny MeSH
• sloučeniny stříbra chemie   MeSH

• Publikační typ
• abstrakty MeSH

Metal-based coordination compounds, including the well-known cytostatic drug cisplatin, are widely used in the anticancer therapy. Generally, they exhibit high cytotoxicity not only towards malignant cells, but also towards non-malignant cells, which represents main problem of their clinical use. Herein, we describe the synthesis, characterization and biological testing of three trinuclear nickel(II) coordination compounds. Central nickel atoms are bridged by trithiocyanurate anion and coordinated by triamine and bis-benzimidazoles, respectively. To delineate a potential usage in anticancer therapy, we encapsulated the most cytotoxic complex into biomacromolecular protein cage apoferritin (FRT), forming FRTNi. FRT encapsulation markedly decreased the hemotoxicity of free Ni compounds. Despite FRTNi can be internalized through passive targeting by enhanced permeability and retention effect, we further introduced active targeting utilizing folate receptor (FR) via folic acid (FA)-modified FRT (FRTNiFA). Using breast cancer cell lines T-47D (FR+), MCF-7 (FR-) and non-malignant mammary gland derived cell line HBL-100 (FR-), we show pronounced FR-dependent internalization of FRTNiFA. Overall, we demonstrate that the FRT macromolecular nanocarrier provides a very low off-target toxicity, which could enable the use of highly toxic Ni compounds in cancer nanomedicine.

• MeSH
• apoptóza účinky léků   MeSH
• biokompatibilní materiály farmakologie   MeSH
• buněčná smrt účinky léků   MeSH
• buněčné klony MeSH
• endocytóza účinky léků   MeSH
• ferritiny metabolismus   MeSH
• komplexní sloučeniny chemická syntéza   chemie   farmakologie   MeSH
• kyselina listová farmakologie   MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• nikl farmakologie   MeSH
• pohyb buněk účinky léků   MeSH
• proliferace buněk účinky léků   MeSH
• proteiny vázající železo metabolismus   MeSH
• receptory buněčného povrchu metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• ataxie chemicky indukované   MeSH
• krysa rodu rattus MeSH
• myši MeSH
• piperaziny farmakologie   toxicita   MeSH
• podmiňování (psychologie) účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• myši MeSH
• zvířata MeSH