The current study explores the synergistic application of biophysical chemistry and nanotechnology in therapeutic treatments, focusing specifically on the development of advanced biomaterials to repurpose FDA-approved Alzheimer's disease (AD) drugs as potent antioxidants. By integration of AD drugs into graphene oxide (GO) nanocomposites, an attempt to enhance the acetylcholinesterase (AChE) inhibition and increase radical scavenging activity is proposed. This bionano synergy is designed to leverage the unique properties of both the nanomaterial surface and the bioactive compounds, improving treatment effectiveness. The nanocomposites also promise targeted drug delivery, as GO can traverse the blood-brain barrier to inhibit AChE more effectively in AD patients. Furthermore, the drug-GO nanocomposite exhibits enhanced radical scavenging capabilities, offering additional therapeutic benefits. This study also elucidates a molecular level understanding on how the properties of the drugs are modified when integrated into nanocomposites with GO, enabling the development of more effective materials. The interdisciplinary approach presented in this study exploits the potential of nanotechnology to enhance drug delivery systems and achieve superior therapeutic outcomes through bionano synergy.
- MeSH
- acetylcholinesterasa * metabolismus chemie MeSH
- Alzheimerova nemoc farmakoterapie metabolismus MeSH
- cholinesterasové inhibitory * chemie farmakologie MeSH
- grafit * chemie MeSH
- lidé MeSH
- nanokompozity * chemie MeSH
- scavengery volných radikálů chemie farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- acetylcholinesterasa * MeSH
- cholinesterasové inhibitory * MeSH
- grafit * MeSH
- graphene oxide MeSH Prohlížeč
- scavengery volných radikálů MeSH
Nanotechnology is gaining significant attention, with numerous biomedical applications. Silver in wound dressings, copper oxide and silver in antibacterial preparations, and zinc oxide nanoparticles as a food and cosmetic ingredient are common examples. However, adverse effects of nanoparticles in humans and the environment from extended exposure at varied concentrations have yet to be established. One of the drawbacks of employing nanoparticles is their tendency to cause oxidative stress, a significant public health concern with life-threatening consequences. Cardiovascular, renal, and respiratory problems and diabetes are among the oxidative stress-related disorders. In this context, phytoantioxidant functionalized nanoparticles could be a novel and effective alternative. In addition to performing their intended function, they can protect against oxidative damage. This review was designed by searching through various websites, books, and articles found in PubMed, Science Direct, and Google Scholar. To begin with, oxidative stress, its related diseases, and the mechanistic basis of oxidative damage caused by nanoparticles are discussed. One of the main mechanisms of action of nanoparticles was unearthed to be oxidative stress, which limits their use in humans. Secondly, the role of phytoantioxidant functionalized nanoparticles in oxidative damage prevention is critically discussed. The parameters for the characterization of nanoparticles were also discussed. The majority of silver, gold, iron, zinc oxide, and copper nanoparticles produced utilizing various plant extracts were active free radical scavengers. This potential is linked to several surface fabricated phytoconstituents, such as flavonoids and phenols. These phytoantioxidant functionalized nanoparticles could be a better alternative to nanoparticles prepared by other existing approaches.
- MeSH
- antioxidancia chemie farmakologie MeSH
- fytonutrienty chemie farmakologie MeSH
- kovové nanočástice aplikace a dávkování chemie toxicita MeSH
- lidé MeSH
- oxidační stres účinky léků MeSH
- rostlinné extrakty farmakologie MeSH
- scavengery volných radikálů farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antioxidancia MeSH
- fytonutrienty MeSH
- rostlinné extrakty MeSH
- scavengery volných radikálů MeSH
Four gallium(III) complexes, [Ga(ClQ)3]⋅MeOH (1 - MeOH), [Ga(ClQ)3] (1), [Ga(BrQ)3] (2), [Ga(dIQ)3] (3) and [Ga(CQ)3] (4), were prepared (H-ClQ = 5-chloro-8-quinolinol, H-BrQ = 7-bromo-8-quinolinol, H-dIQ = 5,7-diiodo-8-quinolinol, H-CQ = 5-chloro-7-iodo-8-quinolinol) and characterised by elemental analysis, IR and NMR spectroscopy. Single crystal structure analysis of 1 - MeOH confirmed that the complex has a molecular structure with gallium(III) metal ion coordinated in mer-fashion by N- and O-donor atoms of three ClQ ligands. Stability of all complexes in DMSO was proved by 1H NMR spectroscopy. The in vitro antiproliferative activity of 1 was evaluated against the A2780, MBA-MB-231 and HCT116 cell lines. Complex 1 displays higher antiproliferative activity (IC50 values in the range 2.1-6 μm) compared to the ClQ ligand and cisplatin; and a significant selective antiproliferative potency (IC50 = 136 μm, for normal MRC5pd30 cell line). Radical scavenging experiments revealed that complex 1 exhibits the highest antioxidant activity of the prepared complexes as well as the ligands.
- Klíčová slova
- 5,7-Diiodo-8-quinolinol, 5-Chloro-7-iodo-8-quinolinol, 5-Chloro-8-quinolinol, 7-Bromo-8-quinolinol, Antiproliferative activity, Antiradical activity, Gallium(III) complexes,
- MeSH
- chinoliny chemická syntéza farmakologie MeSH
- galium chemie MeSH
- komplexní sloučeniny chemická syntéza farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemická syntéza farmakologie MeSH
- scavengery volných radikálů chemická syntéza farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chinoliny MeSH
- galium MeSH
- komplexní sloučeniny MeSH
- protinádorové látky MeSH
- scavengery volných radikálů MeSH
By understanding the rampant infections of Mycobacterium tuberculosis (Mtb) and inflammations caused due to the generation of radical species during the Mtb infection, a series of (E)-2-(2-allylidenehydrazinyl)thiazole derivatives, with dual-action properties, was designed. The molecules were designed with a considerable variation in LogP, one of the critical parameters in physicochemical properties, and analyzed for their drug-likeness. For the synthesis, a simple, green, and multicomponent one-pot synthesis method was developed. The in vitro inhibition potentials were evaluated against Mtb H37 Rv by the microplate Alamar Blue assay. The results reveal that compound 6 was potent, with a MIC value of 6.5 µg/ml, and showed better interactions with the KasA protein with binding free energy (ΔG) of -9.4 kcal/mol. Also, the radical scavenging properties were studied to establish the dual-action properties of the molecules. Compound 9 exhibited promising antioxidant and nitric oxide radical scavenging activities, with 81.7% and 81.0%, respectively, at 1,000-μg/ml concentration.
- Klíčová slova
- (E)-2-(2-allylidenehydrazinyl)thiazoles, anti-inflammatory, antituberculosis, radical scavenger, β-ketoacyl-ACP synthase,
- MeSH
- antituberkulotika chemická syntéza chemie farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- molekulární modely MeSH
- molekulární struktura MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- racionální návrh léčiv * MeSH
- scavengery volných radikálů chemická syntéza chemie farmakologie MeSH
- thiazoly chemická syntéza chemie farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antituberkulotika MeSH
- scavengery volných radikálů MeSH
- thiazoly MeSH
The cytotoxicity of methacrylate-based biopolymers crosslinked by in situ photopolymerization has been attributed mainly to residual methacrylate monomers released due to incomplete polymerization. The residual monomers, primarily triethyleneglycol dimethacrylate or 2-hydroxyethyl methacrylate, may irritate adjacent tissue, or be released into the bloodstream and reach practically all tissues. Increased production of reactive oxygen species, which may be connected to concomitant glutathione depletion, has been the most noticeable effect observed in vitro following the exposure of cells to methacrylates. Radical scavengers such as glutathione or N-acetylcysteine represent the most important cellular strategy against methacrylate-induced toxicity by direct adduct formation, resulting in monomer detoxification. Reactive oxygen species may participate in methacrylate-induced genotoxic or pro-apoptotic effects and cell-cycle arrest via induction of corresponding molecular pathways in cells. A deeper understanding of the biological mechanisms and effects of methacrylates widely used in various bioapplications may enable a better estimation of potential risks and thus, selection of a more appropriate composition of polymer material to eliminate potentially harmful substances such as triethyleneglycol dimethacrylate.
- Klíčová slova
- HEMA, ROS, TEGDMA, cytotoxicity, genotoxicity,
- MeSH
- acetylcystein farmakologie MeSH
- biokompatibilní materiály chemie toxicita MeSH
- glutathion metabolismus MeSH
- kyseliny polymethakrylové chemie toxicita MeSH
- lidé MeSH
- methakryláty chemie toxicita MeSH
- polyethylenglykoly chemie toxicita MeSH
- reaktivní formy kyslíku metabolismus MeSH
- scavengery volných radikálů farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- acetylcystein MeSH
- biokompatibilní materiály MeSH
- glutathion MeSH
- hydroxyethyl methacrylate MeSH Prohlížeč
- kyseliny polymethakrylové MeSH
- methakryláty MeSH
- polyethylenglykoly MeSH
- reaktivní formy kyslíku MeSH
- scavengery volných radikálů MeSH
- triethylene glycol dimethacrylate MeSH Prohlížeč
AIM: To evaluate the effects of orally administered gadolinium orthovanadate GdVO4:Eu3+ nanoparticles (VNPs) on the course of chronic carrageenan-induced intestinal inflammation. METHODS: Samples of small intestinal tissue were collected from four groups of rats (intact, after administration of VNPs, with carrageenaninduced intestinal inflammation, with carrageenan-induced intestinal inflammation orally exposed to VNPs) to assess the intestinal morphology and HSP90α expression. Levels of seromucoid, C-reactive protein, TNF-α, IL-1β and IL-10 were determined in blood serum. RESULTS: Oral exposure to VNPs was associated with neither elevation of inflammation markers in blood serum nor HSP90α overexpression in the small intestine, i.e. no toxic effects of VNPs were observed. Carrageenan-induced intestinal inflammation was accompanied by higher levels of TNF-α and IL-1β, as well as HSP90α upregulation in the intestinal mucosa, compared with controls. Administration of VNPs to rats with enteritis did not lead to statistically significant changes in concentrations of circulating pro-inflammatory cytokines with the trend towards their increase. CONCLUSION: No adverse effects were observed in rats orally exposed to VNPs at a dose of 20 μg/kg during two weeks. Using the experimental model of carrageenan-induced enteritis, it was demonstrated that VNPs at the dose used in our study did not affect the course of intestinal inflammation.
- Klíčová slova
- HSP90α, carrageenan, intestinal inflammation, nanoparticles, rats,
- MeSH
- C-reaktivní protein účinky léků metabolismus MeSH
- enterokolitida krev chemicky indukované patologie MeSH
- gadolinium farmakologie MeSH
- idiopatické střevní záněty krev patologie MeSH
- interleukin-10 krev MeSH
- interleukin-1beta krev účinky léků MeSH
- karagenan toxicita MeSH
- kovové nanočástice * MeSH
- krysa rodu Rattus MeSH
- modely nemocí na zvířatech MeSH
- orosomukoid účinky léků metabolismus MeSH
- proteiny tepelného šoku HSP90 účinky léků metabolismus MeSH
- scavengery volných radikálů farmakologie MeSH
- střevní sliznice účinky léků metabolismus patologie MeSH
- TNF-alfa krev účinky léků MeSH
- vanadáty farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- C-reaktivní protein MeSH
- gadolinium MeSH
- Hsp90aa1 protein, rat MeSH Prohlížeč
- IL1B protein, rat MeSH Prohlížeč
- interleukin-10 MeSH
- interleukin-1beta MeSH
- karagenan MeSH
- orosomukoid MeSH
- proteiny tepelného šoku HSP90 MeSH
- scavengery volných radikálů MeSH
- TNF-alfa MeSH
- vanadáty MeSH
The influence of various hydroxyl radical scavengers such as methanol, ethanol and dimethyl sulfoxide on radiation sensitivity of prokaryotic cells (bacteria Escherichia coli) and eukaryotic cells (yeast Saccharomyces cerevisiae and V79 cells-Chinese hamster pulmonary fibroblasts) irradiated by 60Co gamma radiation was investigated. The dependence of radiation sensitivity on dose rate in range from 1.8 to 100 Gy h-1 was evaluated. Survival of cells irradiated by increasing dose rates was followed using clonogenic assay. Specific protective effect was found to be a nonmonotonous function of dose rate with typical maximum at the dose rate range from 50 to 55 Gy h-1 in all studied cell types.
- MeSH
- CHO buňky MeSH
- Cricetulus MeSH
- dimethylsulfoxid farmakologie MeSH
- Escherichia coli účinky léků účinky záření MeSH
- ethanol farmakologie MeSH
- fibroblasty účinky léků účinky záření MeSH
- hydroxylový radikál * MeSH
- methanol farmakologie MeSH
- poškození DNA MeSH
- radiační ochrana MeSH
- radioizotopy kobaltu farmakologie MeSH
- radioprotektivní látky farmakologie MeSH
- Saccharomyces cerevisiae účinky léků účinky záření MeSH
- scavengery volných radikálů farmakologie MeSH
- tolerance záření MeSH
- viabilita buněk účinky záření MeSH
- vztah dávky záření a odpovědi MeSH
- záření gama MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Cobalt-60 MeSH Prohlížeč
- dimethylsulfoxid MeSH
- ethanol MeSH
- hydroxylový radikál * MeSH
- methanol MeSH
- radioizotopy kobaltu MeSH
- radioprotektivní látky MeSH
- scavengery volných radikálů MeSH
In order to reduce tissue damage caused by ischemia-reperfusion injury, this study aims to investigate the protective effect and mechanism of ?-lipoic acid on hepatic ischemia-reperfusion injury in rats. The bloodstream of rats was blocked in the left middle and left lateral liver lobes of the liver. Forty rats were randomly divided into two groups: treatment group and injury group. Rats were injected with either 25 mg/1 ml of alpha-lipoic acid (treatment group) or 1 ml of saline (injury group) into the caudal vein 15 min before hepatic ischemia-reperfusion. Rat serum alanine aminotransferase (GPT), glutathione (GSH) and superoxide dismutase (SOD) levels were examined at various time points (1, 3, 6 and 12 h) in both groups. Changes in nuclear factor kappa B P65 (NF-kappaB P65) expression in ischemia-reperfusion liver at various time points after reperfusion (1, 3, 6 and 12 h) were evaluated through immunohistochemistry assay. Changes in macrophage inflammatory protein-2 (MIP-2) mRNA and inducible nitric oxide synthase (iNOS) mRNA expression in ischemic reperfused rat livers were detected by RT-PCR. Serum GPT level was significantly higher in the injury group than in the treatment group (P<0.01). NF-kappaB P65, MIP-2 mRNA and iNOS mRNA expression in ischemic reperfused rat livers were significantly higher in the injury group than in the treatment group (P<0.01). Serum GSH and SOD levels were higher in the treatment group than in the injury group (P<0.01). Alpha-lipoic acid significantly reduced ischemia-reperfusion injury in rat livers. This may be associated to the direct scavenging of oxygen-free radicals, increased GSH production, and the activation of downstream media due to decreased NF-kappaB and GSH consumption.
- MeSH
- chemokin CXCL2 genetika metabolismus MeSH
- cytoprotekce MeSH
- glutathion metabolismus MeSH
- játra krevní zásobení účinky léků metabolismus patologie MeSH
- kyselina lipoová farmakologie MeSH
- modely nemocí na zvířatech MeSH
- nemoci jater genetika metabolismus patologie prevence a kontrola MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- reaktivní formy kyslíku metabolismus MeSH
- reperfuzní poškození genetika metabolismus patologie prevence a kontrola MeSH
- scavengery volných radikálů farmakologie MeSH
- signální transdukce MeSH
- superoxiddismutasa metabolismus MeSH
- synthasa oxidu dusnatého, typ II genetika metabolismus MeSH
- transkripční faktor RelA genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chemokin CXCL2 MeSH
- Cxcl2 protein, rat MeSH Prohlížeč
- glutathion MeSH
- kyselina lipoová MeSH
- Nos2 protein, rat MeSH Prohlížeč
- reaktivní formy kyslíku MeSH
- Rela protein, rat MeSH Prohlížeč
- scavengery volných radikálů MeSH
- superoxiddismutasa MeSH
- synthasa oxidu dusnatého, typ II MeSH
- transkripční faktor RelA MeSH
BACKGROUND: Many factors are involved in Alzheimer's Disease (AD) such as amyloid plaques, neurofibrillary tangles, cholinergic deficit and oxidative stress. To counter the complexity of the disease the new approach for drug development is to create a single molecule able to act simultaneously on different targets. OBJECTIVE: We conceived eight drug likeliness compounds targeting the inhibition of cholinesterases and the scavenging of radicals. METHODS: We synthesised the new molecules by the Passerini multicomponent reaction and evaluated their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) as well as their antioxidant activities by the Oxygen Radical Absorbance Capacity (ORAC) assay. The lipinski's rule for drug likeness and in silico ADME prediction was also performed. RESULTS: Compounds 4f [IC50 (EeAChE) = 0.30 μM; IC50 (eqBuChE) = 0.09 μM; ORAC = 0.64 TE] and 4h [IC50 (EeAChE) = 1 μM; IC50 (eqBuChE) = 0.03 μM; ORAC = 0.50 TE] were identified as hits for further development. CONCLUSION: The Passerini reaction allowed us the facile synthesis of ditarget molecules of interest for the treatment of AD.
- Klíčová slova
- Alzheimer disease, ORAC, antioxidants, cholinesterase, chromone, donepezil, passerini reaction.,
- MeSH
- acetylcholinesterasa metabolismus MeSH
- Alzheimerova nemoc farmakoterapie metabolismus MeSH
- butyrylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory chemická syntéza farmakologie MeSH
- chromony chemická syntéza farmakologie MeSH
- donepezil chemická syntéza farmakologie MeSH
- lidé MeSH
- preklinické hodnocení léčiv MeSH
- scavengery volných radikálů chemická syntéza farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- acetylcholinesterasa MeSH
- butyrylcholinesterasa MeSH
- cholinesterasové inhibitory MeSH
- chromony MeSH
- donepezil MeSH
- scavengery volných radikálů MeSH
Cancer cells generally possess higher levels of reactive oxygen species than normal cells, and this can serve as a possible therapeutic target. In this proof-of-concept study, an antioxidant-inspired drug discovery strategy was evaluated using a hydroxycinnamic acid derivative. The processing of oxidized mixtures of p-coumaric acid methyl ester (pcm) revealed a new antitumor lead, graviquinone. Graviquinone bypassed ABCB1-mediated resistance, induced DNA damage in lung carcinoma cells but exerted DNA protective activity in normal keratinocytes, and modulated DNA damage response in MCF-7 cells. The cytotoxic effect of pcm in MCF-7 cells was potentiated under H2O2-induced oxidative stress, and the formation of graviquinone was confirmed by Fenton's reaction on pcm. In silico density functional theory calculations suggested graviquinone as a kinetic product of pcm-scavenging •OH radicals. Our results demonstrate the pharmacological value of an in situ-formed, oxidative stress-related metabolite of an antioxidant. This might be of particular importance for designing new strategies for antioxidant-based drug discovery.
- MeSH
- chemorezistence účinky léků MeSH
- cyklohexanony farmakologie toxicita MeSH
- hydroxylový radikál chemie MeSH
- kyseliny kumarové chemie metabolismus farmakologie MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- objevování léků MeSH
- oxidace-redukce MeSH
- počítačová simulace MeSH
- poškození DNA účinky léků MeSH
- protinádorové látky farmakologie toxicita MeSH
- scavengery volných radikálů farmakologie toxicita MeSH
- signální transdukce účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 4-coumaric acid methyl ester MeSH Prohlížeč
- cyklohexanony MeSH
- hydroxylový radikál MeSH
- kyseliny kumarové MeSH
- protinádorové látky MeSH
- scavengery volných radikálů MeSH
