Now showing 1 - 7 of 7
  • Publication
    Unexpected reactions of NHC*—CuI and —AgI bromides with potassium thio- or seleno­cyanate
    (International Union of Crystallography, 2019-11) ; ; ;
    The reactions of N-heterocyclic carbene CuI and AgI halides with potassium thio- or seleno­cyanate gave unexpected products. The attempted substitution reaction of bromido­(1,3-dibenzyl-4,5-di­phenyl­imidazol-2-yl­idene)silver (NHC*—Ag—Br) with KSCN yielded bis­[bis­(1,3-dibenzyl-4,5-di­phenyl­imidazol-2-yl­idene)silver(I)] tris­(thio­cyanato)­argentate(I) diethyl ether disolvate, [Ag(C29H24N2)2][Ag(NCS)3]·2C4H10O or [NHC*2Ag]2[Ag(SCN)3]·2Et2O, (1), while reaction with KSeCN led to bis­(μ-1,3-dibenzyl-4,5-diphenyl-2-seleno­imidazole-κ2Se:Se)bis­[bromido­(1,3-dibenzyl-4,5-diphenyl-2-seleno­imid­azole-κSe)silver(I)] di­chloro­methane hexa­solvate, [Ag2Br2(C29H24N2Se)4]·6CH2Cl2 or (NHC*Se)4Ag2Br2·6CH2Cl2, (2), via oxidation of the NHC* fragment to 2-seleno­imidazole. This oxidation was observed again in the reaction of NHC*—Cu—Br with KSeCN, yielding catena-poly[[[(1,3-dibenzyl-4,5-diphenyl-2-seleno­imidazole-κSe)copper(I)]-μ-cyanido-κ2C:N] aceto­nitrile monosolvate], {[Cu(CN)(C29H24N2Se)]·C2H3N}n or NHC*Se—CuCN·CH3CN, (3). Compound (1) represents an organic/inorganic salt with AgI in a linear coordination in each of the two cations and in a trigonal coordination in the anion, accompanied by diethyl ether solvent mol­ecules. The tri-blade boomerang-shaped complex anion [Ag(SCN)3]2− present in (1) is characterized by X-ray diffraction for the first time. Compound (2) comprises an isolated centrosymmetric mol­ecule with AgI in a distorted tetra­hedral BrSe3 coordination, together with di­chloro­methane solvent mol­ecules. Compound (3) exhibits a linear polymeric 1∞[Cu—C≡N—Cu—] chain structure with a seleno­imidazole moiety additionally coordinating to each CuI atom, and completed by aceto­nitrile solvent mol­ecules. Electron densities associated with an additional ether solvent mol­ecule in (1) and two additional di­chloro­methane solvent mol­ecules in (2) were removed with the SQUEEZE procedure [Spek (2015[Spek, A. L. (2015). Acta Cryst. C71, 9-18.]). Acta Cryst. C71, 9–18] in PLATON.
      143Scopus© Citations 1
  • Publication
    Bioorganometallic Chemistry: A Key To New Chemotherapy?
    (Slovak University of Technology, 2009-06-12) ;
    6-Substituted fulvenes are interesting and easily accessible starting materials for the synthesis of novel substituted titanocenes via reductive dimerisation, carbolithiation or hydridolithiation reactions, which are followed by a transmetallation reaction with titanium tetrachloride in the latter two cases. Depending on the substitution pattern, these titanocenes prove to be bioorganometallic anticancer drugs, which have significant potential against advanced or metastatic renal-cell cancer. Patients bearing these stages of kidney cancer have a poor prognosis so far and therefore real progress in the area of metal-based anticancer drugs may come from this simple and effective synthetic approach.
      35
  • Publication
    Novel Carbene-Metal Complexes as Anticancer Drugs and Antibiotics - Potential and Limitations
    (Slovak University of Technology Publishing House, 2015-06-01)
    Benzyl-substituted metallocarbene compounds synthesised during the past 5 years give a new perspective on their activity as antibiotic and antitumoral drugs. N-Heterocyclic carbene (NHC) containing Au and Ru compounds have shown promising anticancer activity in vitro and the Cu derivative WBC4 showed strong cytotoxic efficacy in vivo xenograft studies against difficult to treat renal cell cancer. While the carbene-silver acetate derivative SBC1 failed in vivo as an anticancer drug, the antibacterial derivative SBC3 convinced in vivo and this compound may lead the way towards novel injectable emergency antibiotics against resistant bacteria and fungi.
      58
  • Publication
    Coinage Metal NHC Complexes as Novel Antibiotics and Anticancer Drugs
    (Slovak University of Technology Publishing House, 2017-06-09)
    The synthesis and biological evaluation against cancer cells and pathogenic bacteria as well as fungi of five coinage metal NHC complexes derived from copper (WBC4), silver (SBC1/SBC3) and gold (NHC-Au-Cl/NHC-Au-SR) is reviewed. The NHC ligand for these compounds is 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene or derivatives closely related, since this ligand is proven suitable for drug-like molecules. The NHC-silver acetate complex SBC1 failed as an anticancer drug candidate in vivo, while its highly related compound SBC3 succeeded in vivo as an experimental antibiotic in Galleria mellonella larvae showing survival advantage against pathogenic bacteria and fungi. The corresponding gold complexes of NHC-Au-Cl and NHC-Au-SR (R = thioglucoside) as well as the NHC-copper bromide derivative WBC4 exhibited significant growth inhibition, when tested against xenografted human renal-cell cancer Caki-1 in nude mice; WBC4 showed tolerable toxicity in the form of reversible body weight loss, while the two gold compounds did not induce body weight loss in the xenograft mouse model experiment.
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  • Publication
    NHC*-Gold(I) Bioconjugated to Carbohydrates and Peptides as Targeted Anticancer Drugs
    (Press of Slovak University of Technology, Bratislava, 2019-06-07)
    Targeted delivery of potent cytotoxic drugs to cancer cells minimizes systemic toxicity and potentially avoids side effects. NHC*-Au-Cl has already been proven to be a potent anticancer agent based on the stabilising and lipophilic properties of the 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene (NHC*) ligand. One possibility is the chemoselective thiosugar conjugation to NHC*-Au-Cl in order to have active uptake of the resulting NHC*-Au-SR primarily into tumour tissue through the Warburg effect. In addition, a strategy based on chemoselective cysteine conjugation of NHC*-Au-Cl to human serum albumin or Trastuzumab to potentiate drug-ligand ratio, pharmacokinetics, as well as drug efficacy and safety is presented. These strategies are essential steps forward towards the use of gold-based anticancer agents as targeted therapies.
      126
  • Publication
    NHC-Silver(I) Acetates as Bioorganometallic Anticancer and Antibacterial Drugs
    (Slovak University of Technology, 2011-06-01) ;
    The synthesis of N-heterocyclic carbene (NHC) silver(I) acetate complexes with varying lipophilic benzyl-substituents at the 1 and 3 positions of the (benz)imidazole ring was achieved by reaction of silver(I) acetate with the corresponding (benz)imidazolium bromide or iodide salts. These NHC-silver(I) acetate derivatives exhibit interesting structural motifs in the solid state and proof to be soluble and stable in biological media. The preliminary antibacterial activity of all the compounds was studied against Gram-negative bacteria Escherichia coli, and Gram-positive bacteria Staphylococcus aureus using the Kirby-Bauer disk-diffusion method. Almost all the NHC-silver(I) acetate complexes have shown high antibacterial activity compared to the NHC-precursors. In addition, the NHC-silver complexes had their cytotoxicity investigated through MTT based preliminary in vitro testing on the human renal cancer cell line Caki-1 in order to determine their IC50 values. NHC-silver(I) acetate complexes were found to have IC50 values ranging from 1.2 to 63 M. These values represent improved cytotoxicity against Caki-1, most notably for (1-methyl-3-(4-cyanobenzyl) benzimidazole-2-ylidene) silver(I) acetate (IC50 value = 1.2 M), which is a three times more cytotoxic than cisplatin exhibiting an IC50 value of 3.3 M against this cell line.
      107
  • Publication
    In vivo investigations into the carbene gold anticancer drug candidates NHC*-Au-SCN and NHC*-Au-Scyclo
    The anticancer drug candidate 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene gold(I) thiocyanate (NHC*-Au-SCN) and its cyclohexane thiolate derivative (NHC*-Au-Scyclo) exhibited very good activity against human colon cancer with GI50 values against human HCT116 colon cancer cells of 0.40 and 1.65 μM, respectively. In addition, inhibition of the mammalian thioredoxin reductase (TrxR) was observed with IC50 values of 0.77 ± 0.34 µM for NHC*-Au-SCN and 13 ± 4 µM for NHC*-Au-Scyclo?). This encouraged maximum tolerable dose (MTD) experiments in mice, where MTD values of 10 mg/kg for NHC*-Au-SCN and 30 mg/kg for NHC*-Au-Scyclo were determined with single injections to groups of 2 mice. In the subsequent tumor xenograft experiment NHC*-Au-SCN and NHC*-Au-Scyclo were applied three times at two doses in groups of 6 HCT116 tumor-bearing NMRI:nu/nu mice. The control group comprising 6 mice was treated with the solvent only. NHC*-Au-SCN at the dose of 5 and 10 mg/kg and NHC*-Au-Scyclo at the higher dose of 15 and 30 mg/kg showed tolerability towards the drugs, while no significant body weight loss was seen in both groups. NHC*-Au-SCN exerted only weak antitumoral activity reflected by T/C values of 0.81 and 0.65. The tumor volume growth reduction induced by NHC*-Au-Scyclo was better, with optimal T/C values of 0.58 and 0.31 being observed at doses of 15 mg/kg and 30 mg/kg, respectively. Alterations in dosing and/ or application schedules might further improve the antitumoral activity, particularly for NHC*-Au-Scyclo.
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