Four ruthenium complexes of clinically used zinc ionophore pyrithione and its oxygen analog 2-hydroxypyridine N-oxide were prepared and evaluated as inhibitors of enzymes of the aldo-keto reductase subfamily 1C (AKR1C). The crystal stucture of the novel compounds was determined by single crystal X-ray diffraction, and stability and reactivity of the compounds in biologically relevant water-dmso systems was studied by NMR. A kinetic study assisted with docking simulations showed a mixed type of inhibition consisting of a fast reversible and a slow irreversible step in the case of two organometallic compounds. Both compounds also showed a remarkable selectivity towards AKR1C1 and AKR1C3 which are targets for breast cancer drug design. The organoruthenium complex of ligand pyrithione as well as pyrithione itself also displayed toxicity on hormone-dependent MCF-7 breast cancer cell line with EC50 values in the low micromolar range. This article follows and evolves our research on the topic of metal-based inhibitors of enzymes of the aldo-keto reductase family AKR1C. A wider screening to investigate the potential of different organometallic and coordination fragments of ruthenium was also published by our group in Traven et al., Chemico-Biological Interactions 2015, 234, 349-359.
COBISS.SI-ID: 32724441
Two previously isolated cytotoxic complexes [(η6-p-cymene)Ru(κ2-CF3COCHCOC5H3O)L]n + (L = Cl (1); n = 0, pta (2) (pta = 1,3,5-triaza-7-phosphaadamantane); n = 1) were investigated for their selectivity and ability to interact with DNA G-quadruplex adopted by d[G3ATG3ACACAG4ACG3] whose topology exhibits diagonal, edge-type and double-chain reversal loops. Structural changes were followed using high-resolution NMR techniques in the presence of 1 and 2. Results showed weak interaction between the organoruthenium complexes and G-quadruplex. Moreover, no significant changes in thermal stability were confirmed by a UV-melting assay for both 1 and 2. These findings emphasize that anticancer activity of Ru(II) complexes may not be correlated with binding to nucleic acid like G-quadruplex. This study was published as an effort to further elucidate the possible targets of a selected pair of complexes which displayed the highest anticancer potential amoing their series. These results were published Seršen et al. Journal of Medicinal Chemistry 2015, 58, 3984-3996.
COBISS.SI-ID: 1537001411
Cobalt(II) complexes with a series of non-steroidal anti-inflammatory drugs (diflunisal, flufenamic acid, mefenamic acid and niflumic acid) have been synthesized and characterized with physicochemical and spectroscopic techniques and diverse binding modes have been observed by X-ray analysis of five crystal structures. The complexes have high tight binding affinity to bovine or human serum albumins as revealed by the relatively high binding constants, which indicate their binding to SA and transfer towards their biological targets. The complexes were more active than the corresponding free NSAIDs in regard to the ability to scavenge in vitro DPPH, and especially, hydroxyl and superoxide radicals. DNA-viscosity and cyclic voltammetry experiments indicated that the most possible DNA-binding mode is intercalation, as verified by the EB–displacement ability of the complexes. On the basis of the results derived from the in vitro albumin- and DNA-binding and antioxidant activity studies, the tested complexes may be considered candidates as potential cobalt metallodrugs. Related studies on cobalt and copper complexes with the quinolone antimicrobial agent sparfloxacin, flumequine and gatifloxacin were reported in J. Inorg. Biochem. 2016, 163, 18, RSC Adv. 2016, 6, 19555 and Polyhedron 2016, 119, 359.
COBISS.SI-ID: 1537001155
Relationship between formed "SEI" and electrochemical oxygen reduction reaction (ORR) in organic electrolytes was investigated, characterized and described in the above mentioned paper. Above mentioned study is part of comprehensive study of the electrochemical processes in non-aqueous media. The understanding of these processes is of great importance for the energy storage and conversion in non-aqueous media. Described article was the basis for the understanding of the findings published in article: Connell et al. Chemistry of materials, 2016, 28, 8268-8277.
COBISS.SI-ID: 1536884675
Binary Cu/ZnO methanol synthesis catalysts were prepared by photochemical method, whereby CuO crystallites were chemically anchored on the surface of ZnO support using UV irradiation, and the prepared CuO/ZnO composites were subsequently reduced. The amount of CuO crystallites was varied with the concentration of Cu2 + ions used and the time of UV irradiation in order to obtain a wide range of Cu crystallite size. The activity of the catalysts was evaluated for the methanol synthesis reactions from CO2 and H2 at mild reaction conditions (250 °C; 1 bar), and was compared as a relative activity to the commercial methanol synthesis catalyst (Cu/ZnO/Al2O3). The activity of the prepared catalysts was up to 18-fold higher in comparison with the commercial ones. A superior activity was disclosed in terms of the abundant Cu and ZnO surfaces, exposed to reacting molecules. The size of Cu crystallites greatly influenced the formation of methanol, which is favored over the catalysts with smaller Cu crystallites. The latter is proposed to arise from the high dispersion of Cu crystallites on ZnO support, and thus from the enhanced contact between Cu and ZnO particles. The prepared catalysts also showed a high long-term stability due to the small amount of water and carbon monoxide, produced as a by-product.
COBISS.SI-ID: 5878298