A copper(II) tetrapyrazole-based complex of the composition of [Cu(tpyr)(H2O)(ONO2)]NO3 (1), where tpyr represents a tetradentate N-donor ligand formed by the condensation of 1H-pyrazole-5-carbaldehyde in NaOH/MeOH medium, has been prepared and characterized by elemental analysis, infrared spectroscopy, ultraviolet-visible spectroscopy, mass spectrometry, electron paramagnetic resonance and single-crystal X-ray diffraction. Spectrophotometric measurements demonstrated a remarkable peroxidase activity of the complex, which utilized hydrogen peroxide for the oxidation of phenolic compounds such as guaiacol or 3,5-dichloro-2-hydroxybenzene sulfonic acid. The optimum conditions for this reaction were found at pH 8 in ammonium bicarbonate buffer, although the activity was low but still detectable at pH 5-6 in ammonium acetate. As a peroxidase mimic, the complex exhibited enzyme-like Michaelis-Menten kinetics, showing a hyperbolic dependence of the reaction rate on hydrogen peroxide concentration. The determined Km and kcat values were 651 μmol·l-1 and 6.7 × 10-4 s-1, respectively, compared to 41 μmol·l-1 and 73 s-1 for horseradish peroxidase. EPR spectroscopy of the reaction mixture revealed no change in the copper (II) oxidation state during catalysis, suggesting that the oxidation of guaiacol may occur simultaneously with the reduction of hydrogen peroxide to water at the copper centre.

• Klíčová slova
• Copper(II), Crystal structure, MALDI-TOF, Peroxidase activity, Tetrapyrazole, XPS,
• MeSH
• biomimetické materiály * chemie   MeSH
• kinetika MeSH
• komplexní sloučeniny * chemie   chemická syntéza   MeSH
• krystalografie rentgenová MeSH
• měď * chemie   MeSH
• oxidace-redukce MeSH
• peroxid vodíku chemie   MeSH
• peroxidasa * chemie   MeSH
• pyrazoly * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• komplexní sloučeniny * MeSH
• měď * MeSH
• peroxid vodíku MeSH
• peroxidasa * MeSH
• pyrazoly * MeSH

The novel diiron amine complexes [Fe2Cp2(CO)(NH2R')(μ-CO){μ-CN(Me)(Cy)}]CF3SO3 [R' = H, 3; Cy, 4; CH2CH2NH2, 5; CH2CH2NMe2, 6; CH2CH2(4-C6H4OMe), 7; CH2CH2(4-C6H4OH), 8; Cp = η5-C5H5, Cy = C6H11 = cyclohexyl] were synthesized in 49-92 % yields from [Fe2Cp2(CO)2(μ-CO){μ-CN(Me)(Cy)}]CF3SO3, 1a, using a straightforward two-step procedure. They were characterized by IR and multinuclear NMR spectroscopy, and the structure of 7 was confirmed through X-ray diffraction analysis. Complexes 3-8 and the acetonitrile adducts [Fe2Cp2(CO)(NCMe)(μ-CO){μ-CN(Me)(R)}]CF3SO3 (R = Cy, 2a; Me, 2b; Xyl = 2,6-C6H3Me2, 2c) were assessed for their water solubility, octanol-water partition coefficient and stability in physiological-like solutions. The in vitro antiproliferative activity of 2a-c and 3-8 was tested on seven human cancer cell lines (A2780, A2780R, PC3, A549, MCF7, HOS and HT-29), while the selectivity was evaluated using normal MRC-5 cells. Overall, the complexes exhibited variable cytotoxicity, with IC50 values reaching the low micromolar range for 3, 7 and 8 in A2780 and A2780R cells, along with significant selectivity. Targeted experiments covered cell cycle modification, induction of cell death, mitochondrial membrane potential, ROS production and interaction with DNA and bovine serum albumin (BSA) as a model protein. The interaction of 3 with BSA was further investigated through computational studies. Results showed a negligible increase in intracellular ROS levels (except for 2b) and insignificant changes in mitochondrial membrane potential.

• Klíčová slova
• Bioorganometallic chemistry, Cellular effects, Diiron complexes, In vitro cytotoxicity, Labile ligand,
• MeSH
• aminy chemie   farmakologie   MeSH
• komplexní sloučeniny chemie   farmakologie   chemická syntéza   MeSH
• lidé MeSH
• ligandy MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• proliferace buněk * účinky léků   MeSH
• protinádorové látky * farmakologie   chemie   chemická syntéza   MeSH
• screeningové testy protinádorových léčiv * MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• železo chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminy MeSH
• komplexní sloučeniny MeSH
• ligandy MeSH
• protinádorové látky * MeSH
• železo MeSH

The copper(II), cobalt(II), and zinc(II) complexes with 2-(1H-benzimidazol-2-ylmethylsulfanylmethyl)-1H-benzimidazole (tbb) and 2-[2-[2-(1H-benzimidazol-2-yl)ethylsulfanyl]ethyl]-1H-benzimidazole (tebb), [Cu(tbb)Cl2] (1), [Co(tbb)Cl2] (2), [Zn(tbb)Cl2] (3), [Cu(tebb)Cl(H2O)]Cl (4), [Co(tebb)Cl2]n·nCH3OH (5) and [Zn(tebb)Cl(H2O)]Cl (6), have been prepared and evaluated for antiproliferative activity. The structure of (4) was proved by X-ray diffraction crystallography. The coordination compounds were tested for their cytotoxic activities in cancer cell lines in vitro. The lower IC50 values were obtained for Co(II), Cu(II), and Zn(II) complexes with tebb in comparison with tbb complexes. Complex 2 showed strong antiproliferative selectivity for leukemia CEM cells and nontoxicity towards other tested cell lines and normal human cells (BJ and RPE-1). Proapoptotic activity of 2 and 5 were weaker than positive control cisplatin, but the big advantage of these complexes was their zero-cytotoxicity for normal healthy cells in contrast to the high cytotoxicity of cisplatin. The activation of apoptotic initiation phase was detected in neuroblastoma cancer cell line SH-SY5Y where 5 was cytotoxic without fragmentation of cells. Interestingly, complexes 5, 6, and tebb, together with cisplatin, dramatically impaired the mitochondrial membrane potential of SH-SY5Y after 72 h. Taken together, we demonstrated that our compounds trigger apoptosis via the mitochondrial pathway.

• Klíčová slova
• Antiproliferative activity, Apoptosis, Benzimidazole, Biocompatibility, Coordination compound, Mitochondria,
• MeSH
• apoptóza * účinky léků   MeSH
• benzimidazoly * chemie   farmakologie   MeSH
• kobalt chemie   farmakologie   MeSH
• komplexní sloučeniny * farmakologie   chemie   chemická syntéza   MeSH
• krystalografie rentgenová MeSH
• lidé MeSH
• měď chemie   farmakologie   MeSH
• mitochondrie * metabolismus   účinky léků   MeSH
• nádorové buněčné linie MeSH
• protinádorové látky * farmakologie   chemie   chemická syntéza   MeSH
• zinek chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzimidazoly * MeSH
• kobalt MeSH
• komplexní sloučeniny * MeSH
• měď MeSH
• protinádorové látky * MeSH
• zinek MeSH

A series of eight gold(I) N-heterocyclic carbene (NHC) complexes [Au(IMes)(Ln)] based on 1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene (IMes) and 7-azaindole derivatives (HLn), where n = 1-8 for HL1 = 5-fluoro-7-azaindole, HL2 = 5-bromo-7-azaindole, HL3 = 3-chloro-7-azaindole, HL4 = 3-iodo-7-azaindole, HL5 = 5-bromo-3-chloro-7-azaindole, HL6 = 5-bromo-3-iodo-7-azaindole, HL7 = 4-chloro-2-methyl-7-azaindole and HL8 = 7-azaindole, was prepared, characterised and studied for their in vitro anti-cancer and anti-inflammatory effects. The complexes showed significant cytotoxicity on human ovarian cancer cell lines (A2780, IC50 ≈ 8-19 μM and A2780R, IC50 ≈ 8-19 μM) and lowered toxicity in normal HaCat and MRC-5 cells. Cellular effects of the selected complexes 1 and 7 were evaluated in A2780 cells using flow cytometry. Moreover, the time-dependent cellular uptake in A2780 cells, a shotgun proteomic analysis, an ESI-MS study of hydrolysis and interactions with l-cysteine and reduced glutathione (GSH) were performed. Complexes 1 and 7 revealed remarkable anti-inflammatory effects via inhibition of NF-κB activity in human endothelial cells.

• Klíčová slova
• A2780, Anti-inflammatory, Cellular effects, Cytotoxicity, Gold, NHC, Proteomics,
• MeSH
• antiflogistika * farmakologie   chemie   MeSH
• antioxidancia * farmakologie   chemie   MeSH
• apoptóza * účinky léků   MeSH
• endoteliální buňky účinky léků   metabolismus   MeSH
• heterocyklické sloučeniny * chemie   farmakologie   MeSH
• komplexní sloučeniny farmakologie   chemie   chemická syntéza   MeSH
• lidé MeSH
• methan * analogy a deriváty   chemie   farmakologie   MeSH
• nádorové buněčné linie MeSH
• protinádorové látky * farmakologie   chemie   chemická syntéza   MeSH
• zlato * chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika * MeSH
• antioxidancia * MeSH
• carbene MeSH Prohlížeč
• heterocyklické sloučeniny * MeSH
• komplexní sloučeniny MeSH
• methan * MeSH
• protinádorové látky * MeSH
• zlato * MeSH

In this study, three dinuclear copper(II) complexes of ligand 2,6-bis[(N-methyl-piperazine-1-yl)methyl]-4-formyl phenol (L1) and one of 2,6-bis[(N-methylpiperazine-1-yl)methyl]-4-formyl phenol dimethylacetal (L2) with copper(II) ions have been investigated as new types of biomimetic catalysts for the oxidative transformation of different aminophenols and phenyldiamines. All the complexes of interest were newly synthesized and further characterized by IR spectroscopy, UV-Vis and mass spectrometry, X-ray diffraction, and selected electrochemical measurements. Crystal structures of these dinuclear copper(II) complexes have revealed that the coordination-shell geometry of copper atoms is close to a tetragonal pyramid. Catecholase, phenoxazinone synthase, and horseradish peroxidase-like activities were observed in pure methanol and water-methanol mixtures in the presence of molecular oxygen. The potential applicability of the complexes under study is discussed with respect to their possibilities and limitations in the replacement of natural copper-containing oxidoreductases in the oxidative degradation of water-insoluble chlorinated aminophenols in the dye industry or in the production of phenoxazine-based drugs.

• Klíčová slova
• biomimetic catalysis, dinuclear copper(II) complexes, organic dyes, oxidative transformation, pharmaceuticals,
• MeSH
• barvicí látky chemie   MeSH
• biomimetické materiály chemie   chemická syntéza   MeSH
• katalýza MeSH
• katecholoxidasa metabolismus   chemie   MeSH
• komplexní sloučeniny * chemie   chemická syntéza   MeSH
• křenová peroxidasa metabolismus   chemie   MeSH
• krystalografie rentgenová MeSH
• ligandy MeSH
• měď * chemie   MeSH
• oxidace-redukce MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• barvicí látky MeSH
• katecholoxidasa MeSH
• komplexní sloučeniny * MeSH
• křenová peroxidasa MeSH
• ligandy MeSH
• měď * MeSH

The new diiron complexes [Fe2Cp2(CO)(L)(μ-CO){μ-CN(Me)(Cy)}]CF3SO3 (L = pyridine, 3a; 4-aminopyridine, 3b; 4-dimethylaminopyridine, 3c; 4-trifluoromethylpyridine, 3d; nicotinic acid, 4; Cp = η5-C5H5, Cy = C6H11 = cyclohexyl) were synthesized in moderate to high yields using two distinct synthetic routes from the precursors 1 (L = CO, for 4) and 2 (L = NCMe, for 3a-d), respectively. All products were characterized by IR and multinuclear NMR spectroscopy, and the structures of 3b and 3d were ascertained by X-ray diffraction studies. The behavior of the complexes in aqueous solutions (solubility, Log Pow, stability) was assessed using NMR and UV-Vis methods. The in vitro antiproliferative activity of 3a-c and 4 was evaluated against seven human cancer cell lines (A2780, A2780R, A549, MCF-7, PC3, HOS and HT-29) and one normal cell line (MRC-5), following 24 h of incubation (MTT test). Overall, 3-4 demonstrated stronger cytotoxicity than cisplatin, with 3c emerging as the most potent compound. The activity seems primarily linked to the inhibition of metabolic processes in the cancer cells, including depletion of reactive oxygen species (ROS) levels. However, subtle differences have been observed between the complexes, with 4 exerting its cytotoxicity through a distinct multimodal mechanism.

• Klíčová slova
• Bioorganometallic chemistry, Cellular effects, Diiron complexes, In vitro cytotoxicity, Metals in medicine, Pyridine ligand,
• MeSH
• komplexní sloučeniny * chemie   farmakologie   chemická syntéza   MeSH
• krystalografie rentgenová MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky * farmakologie   chemie   chemická syntéza   MeSH
• pyridiny * chemie   farmakologie   MeSH
• screeningové testy protinádorových léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• komplexní sloučeniny * MeSH
• ligandy MeSH
• protinádorové látky * MeSH
• pyridine MeSH Prohlížeč
• pyridiny * MeSH

The acidobasic and complexing properties of 1-methyl-2-mercaptoimidazole (Methimazole, an anti-thyroid drug) were investigated. The pKa 11.49 ± 0.03 was estimated by molecular absorption spectroscopy (I = 0.10 M NaCl, t = 25.0 ± 0.1 °C). This value is in good agreement with the value 11.58 ± 0.05, obtained using the solvent-extraction technique. Theoretical (LFER and quantum chemical calculations) and experimental (1H/13C NMR spectroscopy) methods confirmed that the ligand prefers to be in the thion form, and the proton dissociation takes place on the nitrogen atom. Using glass electrode potentiometry, the complexation of the Pd(II) ion by the methimazole ligand occurs without the participation of protons. The best chemical model considers the [Pd(HL)]2+, [Pd(HL)2]2+ and [Pd(HL)3]2+ complex species, whose stability constants were also determined using spectroscopy and capillary zone electrophoretic (CZE) measurements. The metal complexes dissociate at -log [H+] > 7, where an uncharged palladium(II) hydroxide is formed. The formation kinetics of the palladium(II) complex with methimazole were studied in perchloric and hydrochloric acids (I = 1.00 M, t = 15-40 °C) and the determined rate constants and activation parameters are consistent with literature values determined for the reactions of the Pd(II) ion with thiourea derivatives. The rate constants decrease by two orders of magnitude in both media, which can be assigned to a lower tendency of the chloride ion to dissociate from the [PdCl4]2- complex species than the water molecule from the [Pd(H2O)4]2+ ion. The presented results can be utilized for the design of new Pd and Pt metallodrugs.

• Klíčová slova
• Anti-thyroid drug (methimazol, tapazol): 1-methyl-2-mercaptoimidazole, Complexation properties, Equilibria/kinetics, Metallodrug, Pd(II) ion, Protonation,
• MeSH
• kinetika MeSH
• komplexní sloučeniny * chemie   chemická syntéza   MeSH
• methimazol * chemie   MeSH
• palladium * chemie   MeSH
• termodynamika * MeSH
• thyreostatika chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• komplexní sloučeniny * MeSH
• methimazol * MeSH
• palladium * MeSH
• thyreostatika MeSH

Two In(III) - pyridinecarboxylates ([In(Pic)2(NO3)(H2O)] (InPic; HPic = picolinic acid), [In(HDpic)(Dpic)(H2O)2]·5H2O (InDpic; H2Dpic = dipicolinic acid), have been synthesized by one-step procedure. The complexes composition was confirmed by physicochemical analyses and X-ray diffraction confirmed molecular structure of both complexes. Moreover, complex species speciation was described in both systems by potentiometry and 1H NMR spectroscopy and mononuclear complex species were determined; [In(Pic)]2+ (logβ011 = 6.94(4)), [In(Pic)2]+ (logβ021 = 11.98(9)), [In(Dpic)]+ (logβ011 = 10.42(6)), [In(Dpic)2]- (logβ021 = 17.58(7)) and [In(Dpic)2(OH)]2- (logβ-121 = 10.18(6)). To confirm the complexes stability in 1 % DMSO, 1H NMR spectra were measured (immediately after dissolution up to 96 h). Antimicrobial and anticancer assays indicate a more significant sensitivity of S. aureus bacteria and MDA-MB-231 cancer cells to the InPic complex (IC50 = 25 and 340.7 μM) than to the InDpic (IC50 = 50 and 975.4 μM). The interaction and binding mechanism of picolinic/dipicolinic acid and their indium(III) complexes with HSA (human serum albumin) were studied using fluorescence and CD spectroscopy. The results confirmed that the studied compounds had bound successfully to HSA, and the binding parameters and constants (KSV, Kq, Kb) were calculated together with the number of binding sites. The binding forces were identified based on calculated thermodynamic parameters (ΔG, ΔH, ΔS). Synchronous spectra were used to study the microenvironment of Tyr and Trp residues and displacement assays revealed that site I was the preferred binding site. After binding, conformational changes were found to have occurred in the HSA molecule and the % α-helical content had decreased.

• Klíčová slova
• Anticancer, Antimicrobial, HSA binding, In(III) complexes, Potentiometry, Pyridinecarboxylates, Stability,
• MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• komplexní sloučeniny chemie   chemická syntéza   MeSH
• kyseliny pikolinové * chemie   MeSH
• lidé MeSH
• lidský sérový albumin * chemie   metabolismus   MeSH
• nádorové buněčné linie MeSH
• protinádorové látky chemie   farmakologie   chemická syntéza   MeSH
• Staphylococcus aureus účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• dipicolinic acid MeSH Prohlížeč
• komplexní sloučeniny MeSH
• kyseliny pikolinové * MeSH
• lidský sérový albumin * MeSH
• picolinic acid MeSH Prohlížeč
• protinádorové látky MeSH

Dinuclear complex [Ir2(μ-L1)(η5-Cp*)2Cl2](PF6)2 (1) exhibits low micromolar cytotoxic activity in vitro in various human cancer cells (GI50 = 1.7-3.0 μM) and outperformed its mononuclear analogue [Ir(η5-Cp*)Cl(L2)]PF6 (2; GI50 > 40.0 μM); Cp* = pentamethylcyclopentadienyl, L1 = 4-chloro-2,6-bis[5-(pyridin-2-yl)-1,3,4-thiadiazol-2-yl]pyridine, L2 = 5-(pyridin-2-yl)-1,3,4-thiadiazol-2-amine. Compound 1 upregulated the Keap1/Nrf2 oxidative stress-protective pathway in the treated MV4-11 acute myeloid leukemia cells. In connection with the redox-mediated mode of action of 1, its NADH-oxidizing activity was detected in solution (1H NMR), while NAD+ remained intact (with formate as a hydride source). Surprisingly, only negligible NADH oxidation was detected in the presence of the reduced glutathione and ascorbate. Following the results of in-solution experiments, NAD(H) concentration was assessed in 1-treated MV4-11 cancer cells. Besides the intracellular NADH oxidation in the presence of 1, the induced oxidative stress also led to a decrease of NAD+, resulting in depletion of both NAD+/NADH coenzymes. The discussed findings provide new insight into the biochemical effects of catalytic anticancer compounds that induce cell death via a redox-mediated mode of action.

• Klíčová slova
• Antiproliferative activity, Complex, Dinuclear, Iridium, NADH, Reactive oxygen species,
• MeSH
• faktor 2 související s NF-E2 * metabolismus   MeSH
• iridium * chemie   farmakologie   MeSH
• komplexní sloučeniny farmakologie   chemie   chemická syntéza   MeSH
• lidé MeSH
• NAD * metabolismus   MeSH
• nádorové buněčné linie MeSH
• oxidace-redukce MeSH
• oxidační stres účinky léků   MeSH
• protinádorové látky * farmakologie   chemie   chemická syntéza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktor 2 související s NF-E2 * MeSH
• iridium * MeSH
• komplexní sloučeniny MeSH
• NAD * MeSH
• NFE2L2 protein, human MeSH Prohlížeč
• protinádorové látky * MeSH

Herein, we describe and investigate biological activity of three octahedral ruthenium(II) complexes of the type [Ru(C∧N)(phen)2]+, RuL1-RuL3, containing a π-expansive cyclometalating substituted benzo[g]quinoxaline ligand (C∧N ligand) (phen = 1,10-phenanthroline). Compounds RuL1-RuL3 in cervical, melanoma, and colon human cancer cells exhibit high phototoxicity after irradiation with light (particularly blue), with the phototoxicity index reaching 100 for the complex RuL2 in most sensitive HCT116 cells. RuL2 accumulates in the cellular membranes. If irradiated, it induces lipid peroxidation, likely connected with photoinduced ROS generation. Oxidative damage to the fatty acids leads to the attenuation of the membranes, the activation of caspase 3, and the triggering of the apoptotic pathway, thus implementing membrane-localized photodynamic therapy. RuL2 is the first photoactive ruthenium-based complex capable of killing the hardly treatable colon cancer stem cells, a highly resilient subpopulation within a heterogeneous tumor mass, responsible for tumor recurrence and the metastatic progression of cancer.

• MeSH
• apoptóza účinky léků   MeSH
• buněčná membrána účinky léků   metabolismus   MeSH
• chinoxaliny * chemie   farmakologie   chemická syntéza   MeSH
• fotochemoterapie * MeSH
• fotosenzibilizující látky * farmakologie   chemie   chemická syntéza   terapeutické užití   MeSH
• komplexní sloučeniny * farmakologie   chemie   chemická syntéza   terapeutické užití   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádorové kmenové buňky * účinky léků   patologie   MeSH
• nádory tračníku * farmakoterapie   patologie   MeSH
• protinádorové látky * farmakologie   chemie   chemická syntéza   terapeutické užití   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• ruthenium * chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chinoxaliny * MeSH
• fotosenzibilizující látky * MeSH
• komplexní sloučeniny * MeSH
• protinádorové látky * MeSH
• reaktivní formy kyslíku MeSH
• ruthenium * MeSH