A new zirconium(IV) complex, diaquabis(8-hydroxyquinoline-2-carboxylato-κ3N,O2,O8)zirconium(IV) dimethylformamide disolvate, [Zr(C10H5NO3)2(H2O)2]·2C3H7NO or [Zr(QCa)2(H2O)2]·2DMF (1) (HQCaH is 8-hydroxyquinoline-2-carboxylic acid and DMF is dimethylformamide), was prepared and characterized by elemental analysis, IR spectroscopy and single-crystal X-ray structure analysis. Complex 1 is a mononuclear complex in which the ZrIV atoms sit on the twofold axis and they are octacoordinated by two N and six O atoms of two tridentate anionic QCa2- ligands, and two aqua ligands. Outside the coordination sphere are two DMF molecules bound to the complex unit by hydrogen bonds. The structure and stability of complex 1 in dimethyl sulfoxide were verified by NMR spectroscopy. The cytotoxic properties of 1 and HQCaH were studied in vitro against eight cancer cell lines, and their selectivity was tested on the BJ-5ta noncancerous cell line. Both the complex and HQCaH exhibited low activity, with IC50 > 200 µM. DNA and human serum albumin (HSA) binding studies showed that 1 binds to calf thymus (CT) DNA via intercalation and is able to bind to the tryptophan binding site of HSA (Trp-214).
- Klíčová slova
- 8-hydroxyquinoline-2-carboxylic acid, DNA binding, HSA binding, ZrIV complex, bioactive ligand, crystal structure, cytotoxicity, low-dimensional,
- MeSH
- dimethylformamid MeSH
- DNA chemie MeSH
- komplexní sloučeniny * chemie MeSH
- krystalografie rentgenová MeSH
- lidé MeSH
- lidský sérový albumin MeSH
- ligandy MeSH
- oxychinolin farmakologie MeSH
- vodíková vazba MeSH
- zirkonium * farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dimethylformamid MeSH
- DNA MeSH
- komplexní sloučeniny * MeSH
- lidský sérový albumin MeSH
- ligandy MeSH
- oxychinolin MeSH
- zirkonium * MeSH
BACKGROUND: Cobalt is an essential trace element, but it can also rarely cause cobalt toxicity due to its release from cobalt-containing medical devices. Currently, there are no approved selective cobalt chelators, which would represent an optimal treatment modality. OBJECTIVE: This study aimed to develop a simple and complex methodological approach for screening potential cobalt chelators and evaluating their potential toxicity. METHODS: Firstly, a simple spectrophotometric assay employing 1-nitroso-2-naphthol-3,6- disulfonic acid disodium salt (NNDSA) for screening cobalt chelation was standardized at a pathophysiologically relevant range of pH 4.5-7.5. Then, the suitability of the method was verified using four known metal chelators (EDTA, 8-hydroxyquinoline, chloroxine and nitroxoline). As cobalt can catalyse the Fenton reaction, the potential toxicity of cobalt-chelator complexes was also determined by employing a novel HPLC method with coulometric detection. The effect on erythrocyte haemolysis was tested as well. RESULTS: The NNDSA method had high sensitivity enabling the detection of 25-200 nM of cobalt ions depending on pH conditions. Measurements could be carried out in a wide range of wavelengths from 470 to 540 nm. All tested complexes of the selected chelators decreased the rate of the Fenton reaction. Interestingly, chloroxine mixed with cobalt ions caused marked lysis of erythrocytes in contrast to the other compounds. CONCLUSION: The described complex methodological approach could serve as a simple yet precise tool for evaluating novel, effective and safe cobalt chelators.
- Klíčová slova
- Cobalt, Fenton reaction, HPLC, antioxidant, hydroxyl radical, metal toxicity,
- MeSH
- chelátory * MeSH
- ionty MeSH
- kobalt * chemie MeSH
- oxychinolin MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chelátory * MeSH
- ionty MeSH
- kobalt * MeSH
- oxychinolin MeSH
Background: Antimicrobial submicrometer particles are being studied as promising interventions against a wide range of skin conditions, such as fungal or bacterial infections. Aims: To submicronize chloroxine, the crystalline compound 5,7-dichloro-8-hydroxyquinoline, by nanoprecipitation and characterize the resulting assemblies. Methods: The chloroxine particles were stabilized by a nonionic surfactant and were studied by a broth microdilution assay against 20 medically important bacteria and fungi. The intervention was studied using a murine model of skin irritation. Results & conclusion: Chloroxine nanoparticles with a diameter of 600-800 nm exhibit good tolerability in terms of skin irritation in vivo and good antimicrobial activity. Thus, the fabricated formulation shows great promise for interventions for both cutaneous infection control and prophylaxis.
- Klíčová slova
- dermal infections, dermal safety, nanomedicine, nanoparticle-based intervention, submicronization,
- MeSH
- antibakteriální látky chemie MeSH
- antiinfekční látky * farmakologie MeSH
- chlorochinolinoly * MeSH
- mikrobiální testy citlivosti MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antibakteriální látky MeSH
- antiinfekční látky * MeSH
- chlorochinolinoly * MeSH
- chloroxine MeSH Prohlížeč
AIMS: The objective of the study was to evaluate the antimicrobial interactions between two volatile agents, Cinnamomum cassia essential oil (CCEO) and 8-hydroxyquinoline (8-HQ) against Staphylococcus aureus strains in liquid and vapour phases. METHODS AND RESULTS: In vitro antimicrobial effect of CCEO in combination with 8-HQ was evaluated against 12 strains of S. aureus by broth volatilization chequerboard method. Results show additive effects against all S. aureus strains for both phases. In several cases, sums of fractional inhibitory concentration values of our test combinations were lower than 0·6, which can be considered as a strong additive interaction. Moreover, composition of CCEO was analysed by gas chromatography-mass spectrometry analysis. In the CCEO, 26 compounds in total were identified, where (E)-cinnamaldehyde was the predominant compound, followed by cinnamyl acetate, α-copaene, bornyl acetate and caryophyllene. CONCLUSIONS: Results showed additive in vitro growth-inhibitory effect of CCEO and 8-HQ combination against various standard strains and clinical isolates of S. aureus. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on antibacterial effect of 8-HQ and CCEO combination in liquid and vapour phases. Results of the study suggest these agents as potential candidates for development of new anti-staphylococcal applications that can be used in the inhalation therapy against respiratory infections.
- Klíčová slova
- GC-MS, antimicrobial interactions, broth volatilization chequerboard method, chemical composition, fractional inhibitory concentration, volatile compound,
- MeSH
- akrolein analogy a deriváty chemie MeSH
- antibakteriální látky farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- oleje prchavé farmakologie MeSH
- oxychinolin farmakologie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- skořicovník čínský chemie MeSH
- Staphylococcus aureus účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- akrolein MeSH
- antibakteriální látky MeSH
- cinnamaldehyde MeSH Prohlížeč
- oleje prchavé MeSH
- oxychinolin MeSH
Wilson's disease is a genetic disorder that causes excessive accumulation of copper in the body, leading to toxic damage, especially in the liver and nervous system. The current treatment cause burdensome side effects. We describe the use of chemically modified biopolymer carriers based on microcrystalline cellulose and chitosan containing the highly specific copper chelator 8-hydroxyquinoline as a new type of therapy for Wilson's disease. The chelators can scavenges copper ions released from food during digestion and copper ions present in secretions in the gastrointestinal tract. Because the chelator is covalently bound to indigestible biopolymer carriers (crosslinked chitosan or modified cellulose), it is not taken up by the gastrointestinal tract and it can be eliminated through the feces, avoiding unwanted side effects. This concept was tested on Wistar rats, which received a radioactive 64CuCl2 solution together with the polymers with covalently bound 8-hydroxyquinoline through a gastric probe. 64Copper complex uptake from the gastrointestinal tract was significantly inhibited by both chelating polymers. With the modified polymers, the presence of 64Cu was detected mostly in the gastrointestinal tract, not in the internal organs. These findings indicate modified cellulose and crosslinked chitosan, with covalently bound 8-hydroxyquinoline exhibited the potential to be excellent therapeutics for treating Wilson's disease.
- Klíčová slova
- Biopolymers, Copper chelators, Copper scavengers, Wilson's disease, treatment,
- MeSH
- celulosa aplikace a dávkování farmakokinetika MeSH
- chitosan aplikace a dávkování farmakokinetika MeSH
- gastrointestinální trakt metabolismus MeSH
- hepatolentikulární degenerace farmakoterapie metabolismus MeSH
- měď MeSH
- oxychinolin aplikace a dávkování farmakokinetika MeSH
- potkani Wistar MeSH
- radioizotopy mědi aplikace a dávkování farmakokinetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- celulosa MeSH
- chitosan MeSH
- Copper-64 MeSH Prohlížeč
- cupric chloride MeSH Prohlížeč
- měď MeSH
- microcrystalline cellulose MeSH Prohlížeč
- oxychinolin MeSH
- radioizotopy mědi MeSH
With aim to develop effective proof-of-concept approach which can be used in a development of new preparations for the inhalation therapy, we designed a new screening method for simple and rapid simultaneous determination of antibacterial potential of plant volatiles in the liquid and the vapour phase at different concentrations. In addition, EVA (ethylene vinyl acetate) capmat™ as vapour barrier cover was used as reliable modification of thiazolyl blue tetrazolium bromide (MTT) assay for cytotoxicity testing of volatiles on microtiter plates. Antibacterial activity of carvacrol, cinnamaldehyde, eugenol, 8-hydroxyquinoline, thymol and thymoquinone was determined against Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae using new broth microdilution volatilization method. The cytotoxicity of these compounds was evaluated using MTT test in lung fibroblast cells MRC-5. The most effective antibacterial agents were 8-hydroxyquinoline and thymoquinone with the lowest minimum inhibitory concentrations (MICs) ranging from 2 to 128μg/mL, but they also possessed the highest toxicity in lung cell lines with half maximal inhibitory concentration (IC50) values 0.86-2.95μg/mL. The lowest cytotoxicity effect was identified for eugenol with IC50 295.71μg/mL, however this compound produced only weak antibacterial potency with MICs 512-1024μg/mL. The results demonstrate validity of our novel broth microdilution volatilization method, which allows cost and labour effective high-throughput antimicrobial screening of volatile agents without need of special apparatus. In our opinion, this assay can also potentially be used for development of various medicinal, agricultural, and food applications that are based on volatile antimicrobials.
- Klíčová slova
- Antibacterial activity, Colorimetric assay, Cytotoxicity, Essential oil, Vapour, Volatilization method,
- MeSH
- akrolein analogy a deriváty chemie MeSH
- antibakteriální látky chemie MeSH
- benzochinony chemie MeSH
- buněčné linie MeSH
- cymeny MeSH
- eugenol chemie MeSH
- fytonutrienty chemie MeSH
- Haemophilus influenzae účinky léků MeSH
- lidé MeSH
- mikrobiální testy citlivosti metody MeSH
- monoterpeny chemie MeSH
- oxychinolin chemie MeSH
- Staphylococcus aureus účinky léků MeSH
- Streptococcus pneumoniae účinky léků MeSH
- těkavé organické sloučeniny chemie MeSH
- tetrazoliové soli MeSH
- thiazoly MeSH
- thymol chemie MeSH
- volatilizace * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- akrolein MeSH
- antibakteriální látky MeSH
- benzochinony MeSH
- carvacrol MeSH Prohlížeč
- cinnamaldehyde MeSH Prohlížeč
- cymeny MeSH
- eugenol MeSH
- fytonutrienty MeSH
- monoterpeny MeSH
- oxychinolin MeSH
- těkavé organické sloučeniny MeSH
- tetrazoliové soli MeSH
- thiazoly MeSH
- thiazolyl blue MeSH Prohlížeč
- thymol MeSH
- thymoquinone MeSH Prohlížeč
Clostridium perfringens-induced necrotic enteritis is generally controlled by antibiotics. However, because of increasing antibiotic resistance, other antibacterial agents are required, preferably ones that do not affect the beneficial intestinal microbiota of the host. This study evaluated the in vitro selective growth-inhibitory effect of 8-hydroxyquinoline (8HQ) on C. perfringens vs. bifidobacteria in a medium containing chicken ileal digesta. Prior to the experiments, the minimum inhibitory concentrations of 8HQ and penicillin G were determined by broth microdilution assay. The minimum inhibitory concentration values of 8HQ for C. perfringens were 16-32 times lower than the values for bifidobacteria. Treatment of autoclaved and non-autoclaved chicken ileal digesta with 8HQ showed a selective anticlostridial effect. After incubation of C. perfringens with autoclaved ileal digesta for 3 h, all 8HQ concentrations tested (32-2048 μg/mL) significantly reduced C. perfringens bacterial count. In contrast, the same treatment had no or only a slight effect on bifidobacteria counts. Unlike 8HQ, penicillin G did not exhibit any selectivity. Similar results were obtained after incubation for 24 h. In non-autoclaved ileal digesta, all 8HQ concentrations tested significantly reduced C. perfringens bacterial counts after incubation for 30 min and 3 h, while no effect was observed on bifidobacteria. These results suggest that 8HQ may serve as a prospective veterinary compound for use against necrotic enteritis in poultry.
- MeSH
- antibakteriální látky farmakologie MeSH
- Bifidobacterium účinky léků MeSH
- Clostridium perfringens účinky léků MeSH
- ileum mikrobiologie MeSH
- klostridiové infekce prevence a kontrola veterinární virologie MeSH
- kur domácí mikrobiologie MeSH
- nemoci drůbeže prevence a kontrola virologie MeSH
- oxychinolin farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- oxychinolin MeSH
Ring-substituted 8-hydroxyquinoline-2-carboxanilides inhibited photosynthetic electron transport (PET) through photosystem (PS) II. Their inhibitory efficiency depended on the compound lipophilicity, the electronic properties of the substituent R and the position of the substituent R on the benzene ring. The most effective inhibitors showing IC50 values in the range 2.3-3.6μM were substituted in C'(3) by F, CH3, Cl and Br. The dependence of the PET-inhibiting activity on the lipophilicity of the compounds was quasi-parabolic for 3-substituted derivatives, while for C'(2) ones a slight increase and for C'(4) derivatives a sharp decrease of the activity were observed with increasing lipophilicity. In addition, the dependence of PET-inhibiting activity on electronic Hammett's σ parameter of the substituent R was observed with optimum σ value 0.06 for C'(4) and 0.34 for C'(3) substituted derivatives, while the value of σ parameter did not significantly influence the PET-inhibiting activity of C'(2) substituted compounds. Interactions of the studied compounds with chlorophyll a and aromatic amino acids present in the pigment-protein complexes mainly in PS II were documented by fluorescence spectroscopy. The section between P680 and plastoquinone QB occurring on the acceptor side of PS II can be suggested as the site of action of the compounds.
- Klíčová slova
- 8-Hydroxyquinolines, Hill reaction, Photosystem II, Structure–activity relationships,
- MeSH
- anilidy chemická syntéza chemie metabolismus MeSH
- chlorofyl a MeSH
- chlorofyl chemie MeSH
- chloroplasty metabolismus MeSH
- fluorescenční spektrometrie MeSH
- fotosyntéza MeSH
- fotosystém II (proteinový komplex) antagonisté a inhibitory metabolismus MeSH
- oxychinolin chemie MeSH
- Spinacia oleracea metabolismus MeSH
- transport elektronů MeSH
- vazba proteinů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- anilidy MeSH
- chlorofyl a MeSH
- chlorofyl MeSH
- fotosystém II (proteinový komplex) MeSH
- oxychinolin MeSH
We discovered a small series of hit compounds that show multitargeting activities against key targets in Alzheimer's disease (AD). The compounds were designed by combining the structural features of the anti-AD drug donepezil with clioquinol, which is able to chelate redox-active metals, thus decreasing metal-driven oxidative phenomena and β-amyloid (Aβ)-mediated neurotoxicity. The majority of the new hybrid compounds selectively target human butyrylcholinesterase at micromolar concentrations and effectively inhibit Aβ self-aggregation. In addition, compounds 5-chloro-7-((4-(2-methoxybenzyl)piperazin-1-yl)methyl)-8-hydroxyquinoline (1 b), 7-((4-(2-methoxybenzyl)piperazin-1-yl)methyl)-8-hydroxyquinoline (2 b), and 7-(((1-benzylpiperidin-4-yl)amino)methyl)-5-chloro-8-hydroxyquinoline (3 a) are able to chelate copper(II) and zinc(II) and exert antioxidant activity in vitro. Importantly, in the case of 2 b, the multitarget profile is accompanied by high predicted blood-brain barrier permeability, low cytotoxicity in T67 cells, and acceptable toxicity in HUVEC primary cells.
- Klíčová slova
- Alzheimer′s disease, antioxidants, chelation, cholinesterases, inhibitors, β-amyloid,
- MeSH
- Alzheimerova nemoc farmakoterapie MeSH
- amyloidní beta-protein antagonisté a inhibitory metabolismus MeSH
- antioxidancia chemie terapeutické užití toxicita MeSH
- butyrylcholinesterasa chemie metabolismus MeSH
- chelátory chemie MeSH
- cholinesterasové inhibitory chemie terapeutické užití toxicita MeSH
- donepezil MeSH
- endoteliální buňky pupečníkové žíly (lidské) MeSH
- hematoencefalická bariéra metabolismus MeSH
- indany chemie terapeutické užití toxicita MeSH
- jodchlorhydroxychin chemie terapeutické užití toxicita MeSH
- lidé MeSH
- měď chemie MeSH
- nádorové buněčné linie MeSH
- oxychinolin chemie terapeutické užití toxicita MeSH
- piperidiny chemie terapeutické užití toxicita MeSH
- racionální návrh léčiv MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zinek chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- amyloidní beta-protein MeSH
- antioxidancia MeSH
- butyrylcholinesterasa MeSH
- chelátory MeSH
- cholinesterasové inhibitory MeSH
- donepezil MeSH
- indany MeSH
- jodchlorhydroxychin MeSH
- měď MeSH
- oxychinolin MeSH
- piperidiny MeSH
- zinek MeSH
UNLABELLED: The need for suitable selective cultivation media for the isolation of Bifidobacterium spp. continues to be a real concern in the field of intestinal microbiology. Isolation of bifidobacteria from human and animal faecal samples using selective agar plating may be problematic especially in samples with increased clostridial counts than bifidobacterial counts. Due to the absence of anticlostridial agents in existing selective media, clostridia can displace bifidobacteria resulting in incorrect estimation of their counts. Therefore, we supplemented the existing selective medium 'modified Wilkins Chalgren agar with mupirocin' (MWM) with 90 mg l(-1) of 8-hydroxyquinoline (8HQ), which was recently proved to act selectively against clostridia. The newly composed 'modified Wilkins-Chalgren agar with 8HQ' (MWMQ) was tested on pure bifidobacterial and clostridial strains, their mixtures, and using faecal samples of mammalian origin; its selectivity was evaluated by genus-specific identification of isolates. The results demonstrated that the presence of 8HQ in this agar eliminated the growth of nonbifidobacterial strains on MWMQ compared to that on MWM, whereas the recovery of bifidobacterial counts was at satisfactory levels. In conclusion, MWMQ could be recommended for bifidobacterial isolation from human and animal faeces especially when bifidobacteria are not numerically dominant and there are chances of clostridial contamination. SIGNIFICANCE AND IMPACT OF THE STUDY: Routine isolation of bifidobacteria from mammalian faeces does not use a reliable selective agar with an anticlostridial agent. Overgrowth of clostridia may result in incorrect estimation of bifidobacterial counts. Thus, in order to improve the selectivity of existing media for bifidobacterial isolation, we chose the modified Wilkins-Chalgren agar with mupirocin and supplemented it with 8-hydroxyquinoline (8HQ), a molecule that shows anticlostridial activity without affecting the growth of bifidobacteria. This newly composed medium showed enhanced selectivity and specificity compared to the original medium and therefore, can be recommended for the isolation of bifidobacteria from mammal faeces.
- Klíčová slova
- 8-quinolinol, Bifidobacterium, Clostridium, intestinal microbiota, isolation, selective agar,
- MeSH
- agar farmakologie MeSH
- bakteriální nálož účinky léků MeSH
- Bifidobacterium růst a vývoj izolace a purifikace MeSH
- Clostridium účinky léků růst a vývoj MeSH
- feces mikrobiologie MeSH
- kultivační média farmakologie MeSH
- lidé MeSH
- mupirocin farmakologie MeSH
- oxychinolin farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- agar MeSH
- kultivační média MeSH
- mupirocin MeSH
- oxychinolin MeSH
