We have synthesized a series of 2-phenyl-3-hydroxy-4(1H)-quinolinone derivatives substituted with one or more fluorine atoms on the quinolone backbone as well as on phenyl ring. The derivatives bearing more fluorine atoms were subjected to modification by nucleophilic substitutions by thiophenol, morpholine, and piperazine derivative. We have tested the prepared compounds in cytotoxic activity assay against cancer cell lines. Four derivatives exhibited micromolar values of IC50 against some of the cancer cell lines, and we have subjected them to cell cycle analysis on CCRF-CEM. Moreover, most active 7-fluoro-3-hydroxy-2-phenyl-6-(phenylthio)quinolin-4(1H)-one inhibits mitosis progression. Cell cycle analysis, in vitro tubulin polymerization assay, and tubulin imaging in cells indicated that the anticancer activity of thiophenol derivative is associated with its ability to inhibit microtubule formation.

• MeSH
• chinolony chemická syntéza   chemie   farmakologie   MeSH
• halogenace MeSH
• HCT116 buňky MeSH
• lidé MeSH
• modulátory tubulinu chemická syntéza   chemie   farmakologie   MeSH
• molekulární struktura MeSH
• polymerizace účinky léků   MeSH
• tubulin metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Currently, one of the most promising treatments of lipopolysaccharides (LPS)-induced sepsis is based on hemofiltration. Nevertheless, proteins rapidly adsorbed on the artificial surface of membranes which leads to activation of coagulation impairing effective scavenging of the endotoxins. To overcome this challenge, we designed polymer-brush-coated microparticles displaying antifouling properties and functionalized them with polymyxin B (PMB) to specifically scavenge LPS the most common endotoxin. Poly[( N-(2-hydroxypropyl) methacrylamide)- co-(carboxybetaine methacrylamide)] brushes were grafted from poly(glycidyl methacrylate) microparticles using photoinduced single-electron transfer living radical polymerization (SET-LRP). Notably, only parts-per-million of copper catalyst were necessary to achieve brushes able to repel adsorption of proteins from blood plasma. The open porosity of the particles, accessible to polymerization, enabled us to immobilize sufficient PMB to selectively scavenge LPS from blood plasma.

• MeSH
• adsorpce MeSH
• akrylamidy metabolismus   MeSH
• biokompatibilní potahované materiály farmakologie   MeSH
• bioznečištění prevence a kontrola   MeSH
• epoxidové sloučeniny metabolismus   MeSH
• krevní plazma metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy metabolismus   MeSH
• methakryláty metabolismus   MeSH
• polymerizace účinky léků   MeSH
• polymery chemie   MeSH
• polymyxin B farmakologie   MeSH
• povrchové vlastnosti účinky léků   MeSH
• proteiny metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Actin cytoskeleton is a vital cellular structure primarily known for controlling cell integrity, division and expansion. Here we present a proteomic dissection of Arabidopsis roots treated by actin depolymerizing agent latrunculin B. Pharmacological disintegration of the actin cytoskeleton by latrunculin B caused downregulation of several proteins involved in the actin organization and dynamics. Moreover, this approach helped to identify new protein candidates involved in gene transcription, due to the altered abundance of proteins involved in mRNA nuclear export. Finally, latrunculin B negatively affected the abundance of abscisic acid (ABA) responsive proteins. SIGNIFICANCE: This article substantially contributes to the current knowledge about the importance of actin organization and dynamics in proteome remodelling. We employed gel based and gel free proteomic analyses and identified several new protein candidates and protein networks linking actin dynamics to the gene transcription and to the ABA response in Arabidopsis.

• MeSH
• aktiny chemie   metabolismus   MeSH
• Arabidopsis chemie   MeSH
• bicyklické sloučeniny heterocyklické farmakologie   MeSH
• kořeny rostlin chemie   MeSH
• kyselina abscisová fyziologie   MeSH
• mikrofilamenta účinky léků   MeSH
• polymerizace účinky léků   MeSH
• proteiny huseníčku analýza   chemie   metabolismus   MeSH
• proteom analýza   účinky léků   MeSH
• proteomika metody   MeSH
• thiazolidiny farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

A substitution of the ammine ligands of cisplatin, cis-[Pt(NH3)2Cl2], for cyclin dependent kinase (CDK) inhibitor bohemine (boh), [2-(3-hydroxypropylamino)-6-benzylamino-9-isopropylpurine], results in a compound, cis-[Pt(boh)2Cl2] (C1), with the unique anticancer profile which may be associated with some features of the damaged DNA and/or its cellular processing (Travnicek Z et al. (2003) J Inorg Biochem94, 307-316; Liskova B (2012) Chem Res Toxicol25, 500-509). A combination of biochemical and molecular biology techniques was used to establish mechanistic differences between cisplatin and C1 with respect to the DNA damage they produce and their interactions with critical DNA-binding proteins, DNA-processing enzymes and glutathione. The results show that replacement of the NH3 groups in cisplatin by bohemine modulates some aspects of the mechanism of action of C1. More specifically, the results of the present work are consistent with the thesis that, in comparison with cisplatin, effects of other factors, such as: (i) slower rate of initial binding of C1 to DNA; (ii) the lower efficiency of C1 to form bifunctional adducts; (iii) the reduced bend of longitudinal DNA axis induced by the major 1,2-GG intrastrand cross-link of C1; (iv) the reduced affinity of HMG domain proteins to the major adduct of C1; (v) the enhanced efficiency of the DNA adducts of C1 to block DNA polymerization and to inhibit transcription activity of human RNA pol II and RNA transcription; (vi) slower rate of the reaction of C1 with glutathione, may partially contribute to the unique activity of C1.

• MeSH
• DNA účinky léků   metabolismus   MeSH
• genetická transkripce účinky léků   MeSH
• HeLa buňky MeSH
• lidé MeSH
• molekulární konformace MeSH
• molekulární struktura MeSH
• organoplatinové sloučeniny chemická syntéza   chemie   farmakologie   MeSH
• polymerizace účinky léků   MeSH
• poškození DNA MeSH
• proteinkinasa CDC2 antagonisté a inhibitory   MeSH
• protinádorové látky chemická syntéza   chemie   farmakologie   MeSH
• puriny chemie   farmakologie   MeSH
• RNA-polymerasa II antagonisté a inhibitory   genetika   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

gamma-Fe2O3 nanoparticles obtained by coprecipitation of Fe(II) and Fe(III) chlorides with a base and subsequent oxidation were coated with a shell of hydrophilic biocompatible poly(N,N-dimethylacrylamide) (PDMAAm). Various initiators were attached to the iron oxide surface to enable the use of the "grafting-from" approach for immobilization of PDMAAm. They included 2,2'-azobis(2-methylpropanimidamide) dihydrochloride (AMPA), 2,2'-azobis(N-hydroxy-2-methylpropanimidamide) dihydrochloride (ABHA) and 4-cyano-4-{[1-cyano-3-(N-hydroxycarbamoyl)-1-methylpropyl]azo}pentanoic acid (CCHPA). Engulfment of PDMAAm-coated y-Fe2O3 nanoparticles by murine J774.2 macrophages was investigated. Only some nanoparticles were engulfed by the macrophages. PDMAAm-AMPA-gamma-Fe2O3 and PDMAAm-ABHA-y-Fe2O3 nanoparticles were rapidly engulfed by the cells. In contrast, neat y-Fe2O3 and PDMAAm-CCHPA-gamma-Fe2O3 particles induced formation of transparent vacuoles indicating toxicity of the particles. Thus, PDMAAm-coated AMPA- and ABHA-gamma-Fe2O3 nanoparticles can be recommended as non-toxic labels for mammalian cells.

• MeSH
• akrylamidy chemie   farmakologie   MeSH
• buněčné linie MeSH
• fluorescenční mikroskopie MeSH
• hydrofobní a hydrofilní interakce účinky léků   MeSH
• magnetické jevy MeSH
• magnety * MeSH
• makrofágy cytologie   účinky léků   metabolismus   MeSH
• myši MeSH
• nanočástice chemie   ultrastruktura   MeSH
• polymerizace účinky léků   MeSH
• radiační rozptyl MeSH
• savci metabolismus   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• světlo MeSH
• velikost částic MeSH
• železité sloučeniny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Microtubules (MTs) are essential for many processes in plant cells. MT-associated proteins (MAPs) influence MT polymerization dynamics and enable them to perform their functions. The molecular chaperone Hsp90 has been shown to associate with MTs in animal and plant cells. However, the role of Hsp90-MT binding in plants has not yet been investigated. Here, we show that Hsp90 associates with cortical MTs in tobacco cells and decorates MTs in the phragmoplast. Further, we show that tobacco Hsp90_MT binds directly to polymerized MTs in vitro. The inhibition of Hsp90 by geldanamycin (GDA) severely impairs MT re-assembly after cold-induced de-polymerization. Our results indicate that the plant Hsp90 interaction with MTs plays a key role in cellular events, where MT re-organization is needed.

• MeSH
• benzochinony farmakologie   MeSH
• fylogeneze MeSH
• makrocyklické laktamy farmakologie   MeSH
• mikrotubuly účinky léků   metabolismus   MeSH
• molekulární sekvence - údaje MeSH
• polymerizace účinky léků   MeSH
• proteiny tepelného šoku HSP90 chemie   izolace a purifikace   metabolismus   MeSH
• rekombinantní proteiny izolace a purifikace   metabolismus   MeSH
• repetitivní sekvence aminokyselin MeSH
• rostlinné proteiny metabolismus   MeSH
• rýže (rod) účinky léků   metabolismus   MeSH
• sekvence aminokyselin MeSH
• tabák cytologie   účinky léků   metabolismus   MeSH
• transport proteinů účinky léků   MeSH
• tubulin metabolismus   MeSH
• vazba proteinů účinky léků   MeSH
• zelené fluorescenční proteiny metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The design of anticancer metallodrugs is currently focused on platinum complexes which form on DNA major adducts that cannot readily be removed by DNA repair systems. Hence, antitumor azolato-bridged dinuclear Pt(II) complexes, such as [{cis-Pt(NH(3))(2)}(2)(μ-OH)(μ-pyrazolate)](2+) (AMPZ), have been designed and synthesized. These complexes exhibit markedly higher toxic effects in tumor cell lines than mononuclear conventional cisplatin. METHODS: Biophysical and biochemical aspects of the alterations induced in short DNA duplexes uniquely and site-specifically modified by the major DNA adduct of AMPZ, namely 1,2-GG intrastrand cross-links, were examined. Attention was also paid to conformational distortions induced in DNA by the adducts of AMPZ and cisplatin, associated alterations in the thermodynamic stability of the duplexes, and recognition of these adducts by high-mobility-group (HMG) domain proteins. RESULTS: Chemical probing of DNA conformation, DNA bending studies and translesion synthesis by DNA polymerase across the platinum adduct revealed that the distortion induced in DNA by the major adduct of AMPZ was significantly less pronounced than that induced by similar cross-links from cisplatin. Concomitantly, the cross-link from AMPZ reduced the thermodynamic stability of the modified duplex considerably less. In addition, HMGB1 protein recognizes major DNA adducts of AMPZ markedly less than those of cisplatin. GENERAL SIGNIFICANCE: The experimental evidence demonstrates why the major DNA adducts of the new anticancer azolato-bridged dinuclear Pt(II) complexes are poor substrates for DNA repair observed in a previously published report. The relative resistance to DNA repair explains why these platinum complexes show major pharmacological advantages over cisplatin in tumor cells.

• MeSH
• adukty DNA chemie   metabolismus   MeSH
• biologické modely MeSH
• cisplatina chemie   metabolismus   farmakologie   MeSH
• denaturace nukleových kyselin účinky léků   MeSH
• diferenciální skenovací kalorimetrie MeSH
• energetický metabolismus fyziologie   MeSH
• konformace nukleové kyseliny MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• molekulární konformace MeSH
• molekulární sondy chemie   MeSH
• organoplatinové sloučeniny chemie   metabolismus   farmakologie   MeSH
• platina chemie   metabolismus   MeSH
• polymerizace účinky léků   MeSH
• protinádorové látky chemie   metabolismus   farmakologie   MeSH
• sekvence nukleotidů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH