A series of novel acridine N-acylhydrazone derivatives have been synthesized as potential topoisomerase I/II inhibitors, and their binding (calf thymus DNA—ctDNA and human serum albumin—HSA) and biological activities as potential anticancer agents on proliferation of A549 and CCD-18Co have been evaluated. The acridine-DNA complex 3b (-F) displayed the highest Kb value (Kb = 3.18 × 103 M−1). The HSA-derivatives interactions were studied by fluorescence quenching spectra. This method was used for the calculation of characteristic binding parameters. In the presence of warfarin, the binding constant values were found to decrease (KSV = 2.26 M−1, Kb = 2.54 M−1), suggesting that derivative 3a could bind to HSA at Sudlow site I. The effect of tested derivatives on metabolic activity of A549 cells evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assay decreased as follows 3b(-F) > 3a(-H) > 3c(-Cl) > 3d(-Br). The derivatives 3c and 3d in vitro act as potential dual inhibitors of hTopo I and II with a partial effect on the metabolic activity of cancer cells A594. The acridine-benzohydrazides 3a and 3c reduced the clonogenic ability of A549 cells by 72% or 74%, respectively. The general results of the study suggest that the novel compounds show potential for future development as anticancer agents.
- Klíčová slova
- HSA binding, acridine, benzohydrazide, ctDNA, spectroscopic study,
- MeSH
- akridiny chemie MeSH
- antitumorózní látky * chemie MeSH
- inhibitory topoisomerasy II farmakologie MeSH
- interkalátory MeSH
- lidé MeSH
- lidský sérový albumin chemie MeSH
- vazebná místa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- akridiny MeSH
- antitumorózní látky * MeSH
- inhibitory topoisomerasy II MeSH
- interkalátory MeSH
- lidský sérový albumin MeSH
The anthracycline (ANT) anticancer drugs such as doxorubicin or daunorubicin (DAU) can cause serious myocardial injury and chronic cardiac dysfunction in cancer survivors. A bisdioxopiperazine agent dexrazoxane (DEX) has been developed as a cardioprotective drug to prevent these adverse events, but it is uncertain whether it is the best representative of the class. The present study used a rabbit model of chronic ANT cardiotoxicity to examine another bisdioxopiperazine compound called GK-667 (meso-(butane-2,3-diylbis(2,6-dioxopiperazine-4,1-diyl))bis(methylene)-bis(2-aminoacetate) hydrochloride), a water-soluble prodrug of ICRF-193 (meso-4,4'-(butan-2,3-diyl)bis(piperazine-2,6-dione)), as a potential cardioprotectant. The cardiotoxicity was induced by DAU (3 mg/kg, intravenously, weekly, 10 weeks), and GK-667 (1 or 5 mg/kg, intravenously) was administered before each DAU dose. The treatment with GK-667 was well tolerated and provided full protection against DAU-induced mortality and left ventricular (LV) dysfunction (determined by echocardiography and LV catheterization). Markers of cardiac damage/dysfunction revealed minor cardiac damage in the group co-treated with GK-667 in the lower dose, whereas almost full protection was achieved with the higher dose. This was associated with similar prevention of DAU-induced dysregulation of redox and calcium homeostasis proteins. GK-667 dose-dependently prevented tumor suppressor p53 (p53)-mediated DNA damage response in the LV myocardium not only in the chronic experiment but also after single DAU administration. These effects appear essential for cardioprotection, presumably because of the topoisomerase IIβ (TOP2B) inhibition provided by its active metabolite ICRF-193. In addition, GK-667 administration did not alter the plasma pharmacokinetics of DAU and its main metabolite daunorubicinol (DAUol) in rabbits in vivo. Hence, GK-667 merits further investigation as a promising drug candidate for cardioprotection against chronic ANT cardiotoxicity.
- Klíčová slova
- ICRF-193, anthracycline cardiotoxicity, bisdioxopiperazine, cardioprotection, dexrazoxane, topoisomerase IIbeta,
- MeSH
- chronická nemoc MeSH
- daunomycin MeSH
- diketopiperaziny farmakologie MeSH
- dysfunkce levé srdeční komory metabolismus patofyziologie prevence a kontrola MeSH
- fibróza MeSH
- funkce levé komory srdeční účinky léků MeSH
- HL-60 buňky MeSH
- inhibitory topoisomerasy II farmakologie MeSH
- kardiomyocyty účinky léků metabolismus patologie MeSH
- kardiomyopatie chemicky indukované metabolismus patofyziologie prevence a kontrola MeSH
- kardiotoxicita MeSH
- králíci MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- poškození DNA * MeSH
- prekurzory léčiv farmakologie MeSH
- remodelace komor účinky léků MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione MeSH Prohlížeč
- daunomycin MeSH
- diketopiperaziny MeSH
- inhibitory topoisomerasy II MeSH
- nádorový supresorový protein p53 MeSH
- prekurzory léčiv MeSH
The bisdioxopiperazine topoisomerase IIβ inhibitor ICRF-193 has been previously identified as a more potent analog of dexrazoxane (ICRF-187), a drug used in clinical practice against anthracycline cardiotoxicity. However, the poor aqueous solubility of ICRF-193 has precluded its further in vivo development as a cardioprotective agent. To overcome this issue, water-soluble prodrugs of ICRF-193 were prepared, their abilities to release ICRF-193 were investigated using a novel UHPLC-MS/MS assay, and their cytoprotective effects against anthracycline cardiotoxicity were tested in vitro in neonatal ventricular cardiomyocytes (NVCMs). Based on the obtained results, the bis(2-aminoacetoxymethyl)-type prodrug GK-667 was selected for advanced investigations due to its straightforward synthesis, sufficient solubility, low cytotoxicity and favorable ICRF-193 release. Upon administration of GK-667 to NVCMs, the released ICRF-193 penetrated well into the cells, reached sufficient intracellular concentrations and provided effective cytoprotection against anthracycline toxicity. The pharmacokinetics of the prodrug, ICRF-193 and its rings-opened metabolite was estimated in vivo after administration of GK-667 to rabbits. The plasma concentrations of ICRF-193 reached were found to be adequate to achieve cardioprotective effects in vivo. Hence, GK-667 was demonstrated to be a pharmaceutically acceptable prodrug of ICRF-193 and a promising drug candidate for further evaluation as a potential cardioprotectant against chronic anthracycline toxicity.
- MeSH
- antracykliny škodlivé účinky MeSH
- dexrazoxan chemie farmakologie MeSH
- diketopiperaziny chemie farmakologie MeSH
- DNA-topoisomerasy typu II metabolismus MeSH
- inhibitory topoisomerasy II chemie farmakologie MeSH
- kardiomyocyty účinky léků metabolismus MeSH
- kardiotonika chemie farmakologie MeSH
- kardiotoxicita farmakoterapie metabolismus MeSH
- králíci MeSH
- piperazin chemie farmakologie MeSH
- prekurzory léčiv chemie farmakologie MeSH
- razoxan chemie farmakologie MeSH
- voda chemie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione MeSH Prohlížeč
- antracykliny MeSH
- dexrazoxan MeSH
- diketopiperaziny MeSH
- DNA-topoisomerasy typu II MeSH
- inhibitory topoisomerasy II MeSH
- kardiotonika MeSH
- piperazin MeSH
- prekurzory léčiv MeSH
- razoxan MeSH
- voda MeSH
A549 human lung carcinoma cell lines were treated with a series of new drugs with both tacrine and coumarin pharmacophores (derivatives 1a-2c) in order to test the compounds' ability to inhibit both cancer cell growth and topoisomerase I and II activity. The ability of human topoisomerase I (hTOPI) and II to relax supercoiled plasmid DNA in the presence of various concentrations of the tacrine-coumarin hybrid molecules was studied with agarose gel electrophoresis. The biological activities of the derivatives were studied using MTT assays, clonogenic assays, cell cycle analysis and quantification of cell number and viability. The content and localization of the derivatives in the cells were analysed using flow cytometry and confocal microscopy. All of the studied compounds were found to have inhibited topoisomerase I activity completely. The effect of the tacrine-coumarin hybrid compounds on cancer cells is likely to be dependent on the length of the chain between the tacrine and coumarin moieties (1c, 1d = tacrine-(CH2)8-9-coumarin). The most active of the tested compounds, derivatives 1c and 1d, both display longer chains.
- Klíčová slova
- A549, DNA, cytotoxicity, lung carcinoma cells, tacrine-coumarin derivatives, topoisomerases I, II,
- MeSH
- antitumorózní látky chemie farmakologie MeSH
- buňky A549 MeSH
- DNA-topoisomerasy I metabolismus MeSH
- DNA-topoisomerasy typu II metabolismus MeSH
- inhibitory topoisomerasy I chemie farmakologie MeSH
- inhibitory topoisomerasy II chemie farmakologie MeSH
- kumariny chemie farmakologie MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- molekulární struktura MeSH
- nádorové buňky kultivované MeSH
- proliferace buněk účinky léků MeSH
- proteiny vázající poly-ADP-ribosu antagonisté a inhibitory metabolismus MeSH
- takrin chemie farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antitumorózní látky MeSH
- DNA-topoisomerasy I MeSH
- DNA-topoisomerasy typu II MeSH
- inhibitory topoisomerasy I MeSH
- inhibitory topoisomerasy II MeSH
- kumariny MeSH
- proteiny vázající poly-ADP-ribosu MeSH
- takrin MeSH
- TOP1 protein, human MeSH Prohlížeč
- TOP2A protein, human MeSH Prohlížeč
Heterocycles have long been the focus of intensive study in attempts to develop novel therapeutic compounds, and acridine, a polynuclear nitrogen molecule containing a heterocycle, has attracted a considerable amount of scientific attention. Acridine derivatives have been studied in detail and have been found to possess multitarget properties, which inhibit topoisomerase enzymes that regulate topological changes in DNA and interfere with the essential biological function of DNA. This article describes some recent advancements in the field of new 9-substituted acridine heterocyclic agents and describes both the structure and the structure-activity relationship of the most promising molecules. The article will also present the IC50 values of the novel derivatives against various human cancer cell lines. The mini review also investigates the topoisomerase inhibition and antibacterial and antimalarial activity of these polycyclic aromatic derivatives.
- Klíčová slova
- 9-substituted acridine, antibacterial, anticancer, antimalarial, topoisomerase II inhibition activity,
- MeSH
- akridiny chemie farmakologie toxicita MeSH
- antibakteriální látky chemie farmakologie toxicita MeSH
- antimalarika chemie farmakologie toxicita MeSH
- antitumorózní látky chemie farmakologie toxicita MeSH
- inhibitory topoisomerasy II chemie farmakologie toxicita MeSH
- lidé MeSH
- nádorové buňky kultivované účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- akridiny MeSH
- antibakteriální látky MeSH
- antimalarika MeSH
- antitumorózní látky MeSH
- inhibitory topoisomerasy II MeSH
Bisdioxopiperazine agent dexrazoxane (ICRF-187) has been the only effective and approved drug for prevention of chronic anthracycline cardiotoxicity. However, the structure-activity relationships (SARs) of its cardioprotective effects remain obscure owing to limited investigation of its derivatives/analogs and uncertainties about its mechanism of action. To fill these knowledge gaps, we tested the hypothesis that dexrazoxane derivatives exert cardioprotection via metal chelation and/or modulation of topoisomerase IIβ (Top2B) activity in chronic anthracycline cardiotoxicity. Dexrazoxane was alkylated in positions that should not interfere with the metal-chelating mechanism of cardioprotective action; that is, on dioxopiperazine imides or directly on the dioxopiperazine ring. The protective effects of these agents were assessed in vitro in neonatal cardiomyocytes. All studied modifications of dexrazoxane molecule, including simple methylation, were found to abolish the cardioprotective effects. Because this challenged the prevailing mechanistic concept and previously reported data, the two closest derivatives [(±)-4,4'-(propane-1,2-diyl)bis(1-methylpiperazine-2,6-dione) and 4-(2-(3,5-dioxopiperazin-1-yl)ethyl)-3-methylpiperazine-2,6-dione] were thoroughly scrutinized in vivo using a rabbit model of chronic anthracycline cardiotoxicity. In contrast to dexrazoxane, both compounds failed to protect the heart, as demonstrated by mortality, cardiac dysfunction, and myocardial damage parameters, although the pharmacokinetics and metal-chelating properties of their metabolites were comparable to those of dexrazoxane. The loss of cardiac protection was shown to correlate with their abated potential to inhibit and deplete Top2B both in vitro and in vivo. These findings suggest a very tight SAR between bisdioxopiperazine derivatives and their cardioprotective effects and support Top2B as a pivotal upstream druggable target for effective cardioprotection against anthracycline cardiotoxicity. SIGNIFICANCE STATEMENT: This study has revealed the previously unexpected tight structure-activity relationships of cardioprotective effects in derivatives of dexrazoxane, which is the only drug approved for the prevention of cardiomyopathy and heart failure induced by anthracycline anticancer drugs. The data presented in this study also strongly argue against the importance of metal-chelating mechanisms for the induction of this effect and support the viability of topoisomerase IIβ as an upstream druggable target for effective and clinically translatable cardioprotection.
- MeSH
- antracykliny škodlivé účinky MeSH
- dexrazoxan farmakologie MeSH
- DNA-topoisomerasy typu II metabolismus MeSH
- HL-60 buňky MeSH
- inhibitory topoisomerasy II farmakologie MeSH
- kardiomyocyty účinky léků metabolismus MeSH
- kardiomyopatie farmakoterapie metabolismus MeSH
- kardiotoxicita farmakoterapie MeSH
- králíci MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- modely u zvířat MeSH
- myokard metabolismus MeSH
- nádorové buněčné linie MeSH
- ochranné látky farmakologie MeSH
- potkani Wistar MeSH
- srdce účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antracykliny MeSH
- dexrazoxan MeSH
- DNA-topoisomerasy typu II MeSH
- inhibitory topoisomerasy II MeSH
- ochranné látky MeSH
A series of new 3,6,9-trisubstituted acridine derivatives with fluorine substituents on phenyl ring were synthesized and their interaction with calf thymus DNA was investigated. Analysis using UV-Vis absorbance spectra provided valuable information about the formation of the acridine-DNA complex. In addition, compounds 8b and 8d were found to display an increased binding affinity (K = 2.32 and 2.28 × 106 M-1, respectively). Topo I/II inhibition mode assays were also performed, and the results verify that the novel compounds display topoisomerase I and II inhibitory activity; compounds 8a, 8b and 8c completely inhibited topoisomerase I activity at a concentration of 60 × 10-6 M, but only compound 8d showed partial ability to inhibit topoisomerase II at concentrations of 30 and 50 × 10-6 M. The ability of the derivatives to impair cell proliferation was tested through an analysis of cell cycle distribution, quantification of cell number, viability studies, metabolic activity measurement and clonogenic assay. The content and localization of the derivatives in cells were analyzed using flow cytometry and fluorescence microscopy. The compounds 8b and 8d altered the physiochemical properties and improved antiproliferative activity in A549 human lung carcinoma cells (compound 8d displayed the highest level of activity, 4.25 × 10-6 M, after 48 h).
- Klíčová slova
- 3,6,9-Trisubstituted acridine derivatives, Cytotoxicity, Fluorine, Lung carcinoma cells, Spectroscopic techniques, calf thymus DNA, topoisomerases I/II,
- MeSH
- akridiny chemická syntéza chemie farmakologie MeSH
- antitumorózní látky chemická syntéza chemie farmakologie MeSH
- buňky A549 MeSH
- DNA-topoisomerasy I metabolismus MeSH
- DNA-topoisomerasy typu II metabolismus MeSH
- DNA účinky léků MeSH
- halogenace MeSH
- inhibitory topoisomerasy I chemická syntéza chemie farmakologie MeSH
- inhibitory topoisomerasy II chemická syntéza chemie farmakologie MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- molekulární struktura MeSH
- proliferace buněk účinky léků MeSH
- skot MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- akridiny MeSH
- antitumorózní látky MeSH
- calf thymus DNA MeSH Prohlížeč
- DNA-topoisomerasy I MeSH
- DNA-topoisomerasy typu II MeSH
- DNA MeSH
- inhibitory topoisomerasy I MeSH
- inhibitory topoisomerasy II MeSH
BACKGROUND: Iron oxide nanoparticles (IONs) have been increasingly utilized in a wide spectrum of biomedical applications. Surface coatings of IONs can bestow a number of exceptional properties, including enhanced stability of IONs, increased loading of drugs or their controlled release. METHODS: Using two-step sonochemical protocol, IONs were surface-coated with polyoxyethylene stearate, polyvinylpyrrolidone or chitosan for a loading of two distinct topo II poisons (doxorubicin and ellipticine). The cytotoxic behavior was tested in vitro against breast cancer (MDA-MB-231) and healthy epithelial cells (HEK-293 and HBL-100). In addition, biocompatibility studies (hemotoxicity, protein corona formation, binding of third complement component) were performed. RESULTS: Notably, despite surface-coated IONs exhibited only negligible cytotoxicity, upon tethering with topo II poisons, synergistic or additional enhancement of cytotoxicity was found in MDA-MB-231 cells. Pronounced anti-migratory activity, DNA fragmentation, decrease in expression of procaspase-3 and enhancement of p53 expression were further identified upon exposure to surface-coated IONs with tethered doxorubicin and ellipticine. Moreover, surface-coated IONs nanoformulations of topo II poisons exhibited exceptional stability in human plasma with no protein corona and complement 3 binding, and only a mild induction of hemolysis in human red blood cells. CONCLUSION: The results imply a high potential of an efficient ultrasound-mediated surface functionalization of IONs as delivery vehicles to improve therapeutic efficiency of topo II poisons.
- Klíčová slova
- doxorubicin, ellipticine, iron oxide, nanoparticles, release kinetics,
- MeSH
- biokompatibilní potahované materiály chemie MeSH
- buněčná smrt účinky léků MeSH
- buněčné linie MeSH
- DNA-topoisomerasy typu II metabolismus MeSH
- doxorubicin farmakologie MeSH
- hojení ran účinky léků MeSH
- inhibitory topoisomerasy II farmakologie MeSH
- kinetika MeSH
- lidé MeSH
- nanočástice chemie MeSH
- pohyb buněk účinky léků MeSH
- povrchové vlastnosti MeSH
- statická elektřina MeSH
- uvolňování léčiv * MeSH
- vibrace ultrazvukové metody MeSH
- železité sloučeniny chemie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biokompatibilní potahované materiály MeSH
- DNA-topoisomerasy typu II MeSH
- doxorubicin MeSH
- ferric oxide MeSH Prohlížeč
- inhibitory topoisomerasy II MeSH
- železité sloučeniny MeSH
Topoisomerase II (TOP2) relieves torsional stress by forming transient cleavage complex intermediates (TOP2ccs) that contain TOP2-linked DNA breaks (DSBs). While TOP2ccs are normally reversible, they can be "trapped" by chemotherapeutic drugs such as etoposide and subsequently converted into irreversible TOP2-linked DSBs. Here, we have quantified etoposide-induced trapping of TOP2ccs, their conversion into irreversible TOP2-linked DSBs, and their processing during DNA repair genome-wide, as a function of time. We find that while TOP2 chromatin localization and trapping is independent of transcription, it requires pre-existing binding of cohesin to DNA. In contrast, the conversion of trapped TOP2ccs to irreversible DSBs during DNA repair is accelerated 2-fold at transcribed loci relative to non-transcribed loci. This conversion is dependent on proteasomal degradation and TDP2 phosphodiesterase activity. Quantitative modeling shows that only two features of pre-existing chromatin structure-namely, cohesin binding and transcriptional activity-can be used to predict the kinetics of TOP2-induced DSBs.
- Klíčová slova
- 3D chromatin organization, DNA double-strand breaks, TDP2, chromosomal translocations, cohesin, proteasome, quantitative modeling, topoisomerase, topoisomerase 2 cleavage complex, transcription,
- MeSH
- chromozomy genetika MeSH
- DNA vazebné proteiny chemie genetika MeSH
- DNA-topoisomerasy typu II chemie genetika MeSH
- DNA chemie genetika MeSH
- dvouřetězcové zlomy DNA * MeSH
- etoposid chemie MeSH
- genetická transkripce MeSH
- genová konverze genetika MeSH
- HCT116 buňky MeSH
- inhibitory topoisomerasy II chemie farmakologie MeSH
- kinetika MeSH
- lidé MeSH
- multiproteinové komplexy chemie genetika MeSH
- oprava DNA genetika MeSH
- proteiny vázající poly-ADP-ribosu chemie genetika MeSH
- torze mechanická MeSH
- translokace genetická genetika MeSH
- zlomy chromozomů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Intramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- DNA-topoisomerasy typu II MeSH
- DNA MeSH
- etoposid MeSH
- inhibitory topoisomerasy II MeSH
- multiproteinové komplexy MeSH
- proteiny vázající poly-ADP-ribosu MeSH
- TOP2A protein, human MeSH Prohlížeč
Nine novel cobalt(III) ternary complexes bearing 4N donor ligands (tris(2-aminoethyl)amine (tren) or tris(2-methylpyridyl)amine (tpa)) and (fluoro)quinolones (quinH) with antibacterial and potential antitumor activity have been synthesized, characterized and screened in various biological assays. The molecular structures of [Co(tpa)(nal)](PF6)2 (3) and [Co(tpa)(nor)(Co(tpa)(norH)](PF6)3(Cl)2∙5MeOH (8) (nal = deprotonated form of nalidixic acid, norH = norfloxacin) with the expected octahedral geometry and (O,O) coordination of the quinolone ligands are also reported. Cyclic voltammetric studies revealed that the 4N donor ligands have much higher effect on the reduction potential of these ternary complexes than the quinolones. Due to the π-back-bonding interaction of the metal ion with the pyridyl-N atoms, the tpa containing compounds demonstrated lower stability and were easier to get reduced in a reversible manner. This character makes them unlikely candidates for development of effective, highly selective hypoxia-activated pro-drug complexes, but this goal might be achieved by substitution of tpa by tren. [Co(tren)(cip)](PF6)2 (4) and [Co(tpa)(cip)](PF6)2 (5) (cip = deprotonated form of ciprofloxacin) showed slightly less antibacterial activity against Escherichia coli than free ciprofloxacin (cipH) and they found to have very low toxicity towards both selected cancer (HeLa, MCF 7, MDA-MB-239) and noncancerous (MRC5 pd30) cells. Interaction of 4 and 5 with calf thymus DNA studied by UV-Vis, flow linear dichroism, viscometry and DNA melting indicated the complexes to bind to DNA as intercalators. DNA electrophoresis revealed that, unlike Co(II) complexes, 4 and 5 are not capable of cleaving DNA, but they can inhibit bacterial DNA gyrase 5 being slightly more active than 4.
- MeSH
- antibakteriální látky chemická syntéza farmakologie toxicita MeSH
- chinolony chemická syntéza farmakologie toxicita MeSH
- ciprofloxacin farmakologie MeSH
- DNA gyráza metabolismus MeSH
- DNA metabolismus MeSH
- inhibitory topoisomerasy II chemická syntéza farmakologie toxicita MeSH
- interkalátory chemická syntéza farmakologie toxicita MeSH
- kobalt chemie MeSH
- komplexní sloučeniny chemická syntéza farmakologie toxicita MeSH
- lidé MeSH
- ligandy MeSH
- mikrobiální testy citlivosti MeSH
- nádorové buněčné linie MeSH
- skot MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antibakteriální látky MeSH
- calf thymus DNA MeSH Prohlížeč
- chinolony MeSH
- ciprofloxacin MeSH
- DNA gyráza MeSH
- DNA MeSH
- inhibitory topoisomerasy II MeSH
- interkalátory MeSH
- kobalt MeSH
- komplexní sloučeniny MeSH
- ligandy MeSH
