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
Tiaprofenic acid is a widely used anti-inflammatory drug; however, the reductive metabolism of tiaprofenic acid is not yet well understood. Here, we compared the reduction of tiaprofenic acid in microsomes and cytosol from the human liver. The microsomes exhibited lower Km value toward tiaprofenic acid than the cytosol (Km = 164 ± 18 μM vs. 569 ± 74 μM, respectively), whereas the cytosol showed higher specific activity during reduction than the microsomes (Vmax = 728 ± 52 pmol mg of protein-1 min-1 vs. 285 ± 11 pmol mg of protein-1 min-1, respectively). Next, a panel of recombinant carbonyl reducing enzymes from AKR and SDR superfamilies has been studied to find the enzymes responsible for the cytosolic reduction of tiaprofenic acid. CBR1 was identified as the reductase of tiaprofenic acid with high specific activity (56,965 ± 6741 pmol mg of protein-1 min-1). Three other enzymes, AKR1A1, AKR1B10, and AKR1C4, were also able to reduce tiaprofenic acid, but with very low activity. Thus, CBR1 was shown to be a tiaprofenic acid reductase in vitro and was also suggested to be the principal tiaprofenic acid reductase in vivo.
- MeSH
- alkoholoxidoreduktasy chemie genetika metabolismus MeSH
- biokatalýza MeSH
- cytosol enzymologie MeSH
- dehydrogenasy/reduktasy s krátkým řetězcem chemie genetika metabolismus MeSH
- játra enzymologie metabolismus MeSH
- kinetika MeSH
- lidé MeSH
- mikrozomy enzymologie MeSH
- propionáty chemie metabolismus MeSH
- rekombinantní proteiny biosyntéza chemie izolace a purifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Enantioseparation performance of two teicoplanin-based chiral stationary phases, Chirobiotic T and Chirobiotic T2, with different teicoplanin coverage and distinct linkage chemistry was compared. Three structurally diverse groups of analytes, amino alcohols (beta-blockers), chlorophenoxypropionic acids, and branched-chain amino acids, in various mobile phase compositions/separation modes were examined. The amino alcohols showed better enantioresolution on Chirobiotic T2 in reverse-phase, hydrophilic interaction chromatography, and polar-ionic mode separation systems. The best results with these analytes were obtained in the polar-ionic mobile phase. In contrast, the chlorophenoxypropionic acids and the branched-chain amino acids yielded an improved enantioresolution on the chiral stationary phase with lower amount of teicoplanin in the hydrophilic interaction chromatography system. The comparison of separation of the chlorophenoxypropionic acids enantiomers in the reverse-phase and hydrophilic interaction chromatography environments showed completely opposite results. While better enantioresolution of chlorophenoxypropionic acids was achieved on Chirobiotic T2 in mobile phases with low methanol content, high methanol concentration was needed to reach baseline enantioseparation on Chirobiotic T.
- MeSH
- aminoalkoholy chemie izolace a purifikace MeSH
- aminokyseliny chemie izolace a purifikace MeSH
- časové faktory MeSH
- molekulární struktura MeSH
- propionáty chemie izolace a purifikace MeSH
- stereoizomerie MeSH
- teikoplanin chemie MeSH
- vysokoúčinná kapalinová chromatografie metody přístrojové vybavení MeSH
- Publikační typ
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Biologically interesting 2-substituted 4-alkylidene pentenolides were prepared with complete control of regio- and stereoselectivity from 2-iodo allylic alcohols via an array of Pd-catalyzed processes, including alkynylation with methyl propiolate, tributyltin hydride addition, and alpha-functionalization. Some of the compounds possess selective cytostatic activity against ovarian carcinoma HeLa S3 and leukemia CCRF-CEM cell lines.
- MeSH
- alkeny chemie MeSH
- antitumorózní látky farmakologie chemická syntéza chemie MeSH
- benzenové deriváty chemie MeSH
- financování organizované MeSH
- inhibiční koncentrace 50 MeSH
- katalýza MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- palladium chemie MeSH
- propionáty farmakologie chemická syntéza chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
