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1.
Molecules ; 29(13)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38998903

RESUMEN

The liver is the main organ responsible for the metabolism of ethanol, which suffers significantly as a result of tissue damage due to oxidative stress. It is known that C60 fullerenes are able to efficiently capture and inactivate reactive oxygen species in in vivo and in vitro systems. Therefore, the purpose of this study is to determine whether water-soluble C60 fullerene reduces the level of pathological process development in the liver of rats induced by chronic alcohol intoxication for 3, 6, and 9 months, depending on the daily dose (oral administration; 0.5, 1, and 2 mg/kg) of C60 fullerene throughout the experiment. In this context, the morphology of the C60 fullerene nanoparticles in aqueous solution was studied using atomic force microscopy. Such biochemical parameters of experimental animal blood as ALT (alanine aminotransferase), AST (aspartate aminotransferase), GGT (gamma-glutamyl transferase) and ALP (alkaline phosphatase) enzyme activities, CDT (carbohydrate-deficient transferrin) level, values of pro-antioxidant balance indicators (concentrations of H2O2 (hydrogen peroxide) and GSH (reduced glutathione), activities of CAT (catalase), SOD (superoxide dismutase) and GPx (selenium-dependent glutathione peroxidase)), and pathohistological and morphometric features of liver damage were analyzed. The most significant positive change in the studied biochemical parameters (up to 29 ± 2% relative to the control), as markers of liver damage, was recorded at the combined administration of alcohol (40% ethanol in drinking water) and water-soluble C60 fullerenes in the optimal dose of 1 mg/kg, which was confirmed by small histopathological changes in the liver of rats. The obtained results prove the prospective use of C60 fullerenes as powerful antioxidants for the mitigation of pathological conditions of the liver arising under prolonged alcohol intoxication.


Asunto(s)
Fulerenos , Hígado , Estrés Oxidativo , Animales , Fulerenos/farmacología , Ratas , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Intoxicación Alcohólica/tratamiento farmacológico , Intoxicación Alcohólica/metabolismo , Ratas Wistar , Nanopartículas/química , Etanol/toxicidad
2.
Int J Mol Sci ; 25(5)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38474314

RESUMEN

The application of a biocompatible polymer nanocarrier can provide target delivery to tumor tissues, improved pharmacokinetics, controlled drug release, etc. Therefore, the proposed strategy was to use the water-soluble star-like copolymers with a Dextran core and Poly(N-isopropylacrylamide) grafts (D-g-PNIPAM) for conjugation with the widely used chemotherapy drugs in oncology-Cisplatin (Cis-Pt) and Doxorubicin (Dox). The molecular characteristics of the copolymer were received using size-exclusion chromatography. The physicochemical characterization of the D-g-PNIPAM-Cis-Pt (or Dox) nanosystem was conducted using dynamic light scattering and FTIR spectroscopy. Using traditional biochemical methods, a comparative analysis of the enhancement of the cytotoxic effect of free Cis-Pt and Dox in combination with D-g-PNIPAM copolymers was performed in cancer cells of the Lewis lung carcinoma line, which are both sensitive and resistant to Dox; in addition, the mechanism of their action in vitro was evaluated.


Asunto(s)
Resinas Acrílicas , Antineoplásicos , Polímeros , Polímeros/química , Agua , Antineoplásicos/uso terapéutico , Doxorrubicina/química , Portadores de Fármacos/química , Micelas
3.
Heliyon ; 9(8): e18745, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37554800

RESUMEN

The C60 fullerene effect (oral administration at a dose of 1 mg kg-1) on the selected biomechanical parameters of muscle gastrocnemius contraction, biochemical indicators of blood and muscle tissue as well as histological changes in rat muscle tissue after chronic alcoholization for 3, 6 and 9 months was studied in detail. Water-soluble C60 fullerenes were shown to reduce the pathological processes development in the muscle apparatus by an average of (35-40)%. In particular, they reduced the time occurrence of fatigue processes in muscle during the long-term development of alcoholic myopathy and inhibited oxidative processes in muscle, thereby preventing its degradation. These findings open up the possibility of using C60 fullerenes as potent antioxidants for the correction of the pathological conditions of the muscle system arising from alcohol intoxication.

4.
BMC Musculoskelet Disord ; 24(1): 606, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37491190

RESUMEN

BACKGROUND: Being a scavenger of free radicals, C60 fullerenes can influence on the physiological processes in skeletal muscles, however, the effect of such carbon nanoparticles on muscle contractility under acute muscle inflammation remains unclear. Thus, the aim of the study was to reveal the effect of the C60 fullerene aqueous solution (C60FAS) on the muscle contractile properties under acute inflammatory pain. METHODS: To induce inflammation a 2.5% formalin solution was injected into the rat triceps surae (TS) muscle. High-frequency electrical stimulation has been used to induce tetanic muscle contraction. A linear motor under servo-control with embedded semi-conductor strain gauge resistors was used to measure the muscle tension. RESULTS: In response to formalin administration, the strength of TS muscle contractions in untreated animals was recorded at 23% of control values, whereas the muscle tension in the C60FAS-treated rats reached 48%. Thus, the treated muscle could generate 2-fold more muscle strength than the muscle in untreated rats. CONCLUSIONS: The attenuation of muscle contraction force reduction caused by preliminary injection of C60FAS is presumably associated with a decrease in the concentration of free radicals in the inflamed muscle tissue, which leads to a decrease in the intensity of nociceptive information transmission from the inflamed muscle to the CNS and thereby promotes the improvement of the functional state of the skeletal muscle.


Asunto(s)
Fulerenos , Ratas , Animales , Fulerenos/farmacología , Ratas Wistar , Agua , Músculo Esquelético , Contracción Muscular , Dolor/tratamiento farmacológico , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Contracción Isométrica
5.
Pharmaceuticals (Basel) ; 15(7)2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35890171

RESUMEN

With the rapid and continuous emergence of antimicrobial resistance, bacterial infections became a significant global healthcare concern. One of the proposed strategies to combat multidrug-resistant pathogens is to use additional compounds, such as natural biologically active substances, as adjuvants for existing antibiotics. In this study, we investigated the potential of caffeine, the widely consumed alkaloid, to modulate the antibacterial effects of antibiotics commonly used in clinical practice. We used disc diffusion assay to evaluate the effects of caffeine on 40 antibiotics in two Staphylococcus aureus strains (methicillin-resistant and methicillin-sensitive). Based on the results of this step, we selected five antibiotics for which the greatest caffeine-induced improvements in antibacterial activity were observed, and further analyzed their interactions with caffeine using a checkerboard approach. Caffeine at concentrations of 250 µg/mL or higher halved the MIC values of ticarcillin, cefepime, gentamycin, azithromycin, and novobiocin for all gram-negative species investigated (Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii). At the highest caffeine concentrations tested (up to 16 mg/mL), decreases in MIC values were 8- to 16-fold. The obtained results prove that caffeine modulates the activity of structurally diverse antibiotics, with the most promising synergistic effects observed for cefepime and azithromycin toward gram-negative pathogens.

6.
Nanomaterials (Basel) ; 12(9)2022 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-35564261

RESUMEN

The development of an effective therapy aimed at restoring muscle dysfunctions in clinical and sports medicine, as well as optimizing working activity in general remains an urgent task today. Modern nanobiotechnologies are able to solve many clinical and social health problems, in particular, they offer new therapeutic approaches using biocompatible and bioavailable nanostructures with specific bioactivity. Therefore, the nanosized carbon molecule, C60 fullerene, as a powerful antioxidant, is very attractive. In this study, a comparative analysis of the dynamic of muscle soleus fatigue processes in rats was conducted using 50 Hz stimulation for 5 s with three consistent pools after intraperitoneal administration of the following antioxidants: C60 fullerene (a daily dose of 1 mg/kg one hour prior to the start of the experiment) and N-acetylcysteine (NAC; a daily dose of 150 mg/kg one hour prior to the start of the experiment) during five days. Changes in the integrated power of muscle contraction, levels of the maximum and minimum contraction force generation, time of reduction of the contraction force by 50% of its maximum value, achievement of the maximum force response, and delay of the beginning of a single contraction force response were analyzed as biomechanical markers of fatigue processes. Levels of creatinine, creatine phosphokinase, lactate, and lactate dehydrogenase, as well as pro- and antioxidant balance (thiobarbituric acid reactive substances, hydrogen peroxide, reduced glutathione, and catalase activity) in the blood of rats were analyzed as biochemical markers of fatigue processes. The obtained data indicate that applied therapeutic drugs have the most significant effects on the 2nd and especially the 3rd stimulation pools. Thus, the application of C60 fullerene has a (50-80)% stronger effect on the resumption of muscle biomechanics after the beginning of fatigue than NAC on the first day of the experiment. There is a clear trend toward a positive change in all studied biochemical parameters by about (12-15)% after therapeutic administration of NAC and by (20-25)% after using C60 fullerene throughout the experiment. These findings demonstrate the promise of using C60 fullerenes as potential therapeutic nanoagents that can reduce or adjust the pathological conditions of the muscular system that occur during fatigue processes in skeletal muscles.

7.
Molecules ; 27(3)2022 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-35164023

RESUMEN

A series of quaternary diammonium salts derivatives of 1,4:3,6-dianhydro-l-iditol were synthesized, using isommanide (1,4:3,6-dianhydro-d-mannitol) as a starting material. Both aromatic (pyridine, 4-(N,N-dimethylamino)pyridine (DMAP), (3-carboxamide)pyridine; N-methylimidazole) and aliphatic (trimethylamine, N,N-dimethylhexylamine, N,N-dimethyloctylamine, N,N-dimethyldecylamine) amines were used, giving eight gemini quaternary ammonium salts (QAS). All salts were tested for their antimicrobial activity against yeasts, Candida albicans and Candida glabrata, as well as bacterial Staphylococcus aureus and Escherichia coli reference strains. Moreover, antibacterial activity against 20 isolates of S. aureus collected from patients with skin and soft tissue infections (n = 8) and strains derived from subclinical bovine mastitis milk samples (n = 12) were evaluated. Two QAS with octyl and decyl residues exhibited antimicrobial activity, whereas those with two decyl residues proved to be the most active against the tested pathogens, with MIC of 16-32, 32, and 8 µg/mL for yeast, E. coli, and S. aureus reference and clinical strains, respectively. Only QAS with decyl residues proved to be cytotoxic in MTT assay against human keratinocytes (HaCaT), IC50 12.8 ± 1.2 µg/mL. Ames test was used to assess the mutagenic potential of QAS, and none of them showed mutagenic activity in the concentration range 4-2000 µg/plate.


Asunto(s)
Compuestos de Amonio Cuaternario , Alcoholes del Azúcar/química , Alcoholes del Azúcar/farmacología , Antiinfecciosos/síntesis química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Candida albicans , Citotoxinas/síntesis química , Citotoxinas/química , Citotoxinas/farmacología , Escherichia coli , Células HaCaT , Humanos , Pruebas de Sensibilidad Microbiana , Pruebas de Mutagenicidad , Mutágenos/síntesis química , Mutágenos/química , Mutágenos/farmacología , Compuestos de Amonio Cuaternario/síntesis química , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/farmacología , Staphylococcus aureus , Alcoholes del Azúcar/síntesis química
8.
Materials (Basel) ; 14(20)2021 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-34683705

RESUMEN

Effective targeting of metastasis is considered the main problem in cancer therapy. The development of herbal alkaloid Berberine (Ber)-based anticancer drugs is limited due to Ber' low effective concentration, poor membrane permeability, and short plasma half-life. To overcome these limitations, we used Ber noncovalently bound to C60 fullerene (C60). The complexation between C60 and Ber molecules was evidenced with computer simulation. The aim of the present study was to estimate the effect of the free Ber and C60-Ber nanocomplex in a low Ber equivalent concentration on Lewis lung carcinoma cells (LLC) invasion potential, expression of epithelial-to-mesenchymal transition (EMT) markers in vitro, and the ability of cancer cells to form distant lung metastases in vivo in a mice model of LLC. It was shown that in contrast to free Ber its nanocomplex with C60 demonstrated significantly higher efficiency to suppress invasion potential, to downregulate the level of EMT-inducing transcription factors SNAI1, ZEB1, and TWIST1, to unblock expression of epithelial marker E-cadherin, and to repress cancer stem cells-like markers. More importantly, a relatively low dose of C60-Ber nanocomplex was able to suppress lung metastasis in vivo. These findings indicated that сomplexation of natural alkaloid Ber with C60 can be used as an additional therapeutic strategy against aggressive lung cancer.

9.
Materials (Basel) ; 14(13)2021 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-34202610

RESUMEN

A new water-soluble thermosensitive star-like copolymer, dextran-graft-poly-N-iso-propilacrylamide (D-g-PNIPAM), was created and characterized by various techniques (size-exclusion chromatography, differential scanning calorimetry, Fourier-transform infrared (FTIR) spectroscopy, and dynamic light scattering (DLS) spectroscopy). The viability of cancer cell lines (human transformed cervix epithelial cells, HeLa) as a model for cancer cells was studied using MTT and Live/Dead assays after incubation with a D-g-PNIPAM copolymer as a carrier for the drug doxorubicin (Dox) as well as a D-g-PNIPAM + Dox mixture as a function of the concentration. FTIR spectroscopy clearly indicated the complex formation of Dox with the D-g-PNIPAM copolymer. The size distribution of particles in Hank's solution was determined by the DLS technique at different temperatures. The in vitro uptake of the studied D-g-PNIPAM + Dox nanoparticles into cancer cells was demonstrated by confocal laser scanning microscopy. It was found that D-g-PNIPAM + Dox nanoparticles in contrast to Dox alone showed higher toxicity toward cancer cells. All of the aforementioned facts indicate a possibility of further preclinical studies of the water-soluble D-g-PNIPAM particles' behavior in animal tumor models in vivo as promising carriers of anticancer agents.

10.
Molecules ; 26(12)2021 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-34198510

RESUMEN

Antimicrobial resistance is a major healthcare threat globally. Xanthines, including caffeine and pentoxifylline, are attractive candidates for drug repurposing, given their well-established safety and pharmacological profiles. This study aimed to analyze potential interactions between xanthines and aromatic antibiotics (i.e., tetracycline and ciprofloxacin), and their impact on antibiotic antibacterial activity. UV-vis spectroscopy, statistical-thermodynamical modeling, and isothermal titration calorimetry were used to quantitatively evaluate xanthine-antibiotic interactions. The antibacterial profiles of xanthines, and xanthine-antibiotic mixtures, towards important human pathogens Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter cloacae were examined. Caffeine and pentoxifylline directly interact with ciprofloxacin and tetracycline, with neighborhood association constant values of 15.8-45.6 M-1 and enthalpy change values up to -4 kJ·M-1. Caffeine, used in mixtures with tested antibiotics, enhanced their antibacterial activity in most pathogens tested. However, antagonistic effects of caffeine were also observed, but only with ciprofloxacin toward Gram-positive pathogens. Xanthines interact with aromatic antibiotics at the molecular and in vitro antibacterial activity level. Given considerable exposure to caffeine and pentoxifylline, these interactions might be relevant for the effectiveness of antibacterial pharmacotherapy, and may help to identify optimal treatment regimens in the era of multidrug resistance.


Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Cafeína/farmacología , Compuestos Heterocíclicos/química , Pentoxifilina/farmacología , Antibacterianos/química , Bacterias/crecimiento & desarrollo , Cafeína/química , Estimulantes del Sistema Nervioso Central/química , Estimulantes del Sistema Nervioso Central/farmacología , Interacciones Farmacológicas , Pruebas de Sensibilidad Microbiana , Pentoxifilina/química , Inhibidores de Fosfodiesterasa/química , Inhibidores de Fosfodiesterasa/farmacología
11.
Int J Mol Sci ; 22(11)2021 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-34064070

RESUMEN

C60 fullerene as a potent free radical scavenger and antioxidant could be a beneficial means for neurodegenerative disease prevention or cure. The aim of the study was to define the effects of C60 administration on mitochondrial dysfunction and oxidative stress disorders in a 3-nitropropionic acid (3-NPA)-induced rat model of Huntington's disease. Animals received 3-NPA (30 mg/kg i.p.) once a day for 3 consecutive days. C60 was applied at a dose of 0.5 mg/kg of body weight, i.p. daily over 5 days before (C60 pre-treatment) and after 3-NPA exposure (C60 post-treatment). Oxidative stress biomarkers, the activity of respiratory chain enzymes, the level of antioxidant defense, and pro- and antiapoptotic markers were analyzed in the brain and skeletal muscle mitochondria. The nuclear and cytosol Nrf2 protein expression, protein level of MnSOD, γ-glutamate-cysteine ligase (γ-GCLC), and glutathione-S-transferase (GSTP) as Nrf2 targets were evaluated. Our results indicated that C60 can prevent 3-NPA-induced mitochondrial dysfunction through the restoring of mitochondrial complexes' enzyme activity, ROS scavenging, modulating of pro/antioxidant balance and GSH/GSSG ratio, as well as inhibition of mitochondria-dependent apoptosis through the limitation of p53 mitochondrial translocation and increase in Bcl-2 protein expression. C60 improved mitochondrial protection by strengthening the endogenous glutathione system via glutathione biosynthesis by up-regulating Nrf2 nuclear accumulation as well as GCLC and GSTP protein level.


Asunto(s)
Fulerenos/fisiología , Mitocondrias/efectos de los fármacos , Enfermedades Mitocondriales/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , Nitrocompuestos/farmacología , Estrés Oxidativo/efectos de los fármacos , Propionatos/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Glutatión/metabolismo , Masculino , Mitocondrias/metabolismo , Enfermedades Mitocondriales/metabolismo , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo
12.
Materials (Basel) ; 14(9)2021 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-33922291

RESUMEN

Doxorubicin, a member of the anthracycline family, is a common anticancer agent often used as a first line treatment for the wide spectrum of cancers. Doxorubicin-based chemotherapy, although effective, is associated with serious side effects, such as irreversible cardiotoxicity or nephrotoxicity. Those often life-threatening adverse risks, responsible for the elongation of the patients' recuperation period and increasing medical expenses, have prompted the need for creating novel and safer drug delivery systems. Among many proposed concepts, polymeric nanocarriers are shown to be a promising approach, allowing for controlled and selective drug delivery, simultaneously enhancing its activity towards cancerous cells and reducing toxic effects on healthy tissues. This article is a chronological examination of the history of the work progress on polymeric nanostructures, designed as efficient doxorubicin nanocarriers, with the emphasis on the main achievements of 2010-2020. Numerous publications have been reviewed to provide an essential summation of the nanopolymer types and their essential properties, mechanisms towards efficient drug delivery, as well as active targeting stimuli-responsive strategies that are currently utilized in the doxorubicin transportation field.

13.
Int J Mol Sci ; 21(18)2020 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-32967212

RESUMEN

Matrix metalloproteinases (MMPs) are extracellular matrix degradation factors, promoting cancer progression. Hence, they could provide an enzyme-assisted delivery of doxorubicin (DOX) in cancer treatment. In the current study, the intercalation process of DOX and tetrapeptide-DOX, the product of the MMPs' cleavage of carrier-linked DOX, into dsDNA was investigated using stationary and time-resolved fluorescence spectroscopy, UV-Vis spectrophotometry and isothermal titration calorimetry (ITC). The molecular dynamics (MD) simulations on the same tetrapeptide-DOX…DNA and DOX…DNA systems were also performed. The undertaken studies indicate that DOX and tetrapeptide-DOX can effectively bond with dsDNA through the intercalation mode; however, tetrapeptide-DOX forms less stable complexes than free DOX. Moreover, the obtained results demonstrate that the differences in DNA affinity of both forms of DOX can be attributed to different intercalation modes. Tetrapeptide-DOX shows a preference to intercalate into DNA through the major groove, whereas DOX does it through the minor one. In summary, we can conclude that the tetrapeptide-DOX intercalation to DNA is significant and that even the lack of non-specific proteases releasing DOX from the tetrapeptide conjugate, the presence of which is suggested by the literature for the efficient release of DOX, should not prevent the cytostatic action of the anthracycline.


Asunto(s)
ADN/química , Doxorrubicina/química , Metaloproteinasas de la Matriz/química , Simulación de Dinámica Molecular , Péptidos/química , Preparaciones de Acción Retardada/química , Humanos
14.
Sci Rep ; 10(1): 9826, 2020 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-32555429

RESUMEN

The fundamental aspects related to the mechanisms of action of C60 fullerene nanoparticles on the level of the central nervous system in different experimental conditions are still unclear. Electrophysiological investigation and immunohistochemical techniques of c-fos expression were combined to determine which neural elements within the lumbar segments and in the central nucleus of the amygdala (CeA) are activated under skeletal muscle fatigue development with prior application of C60 fullerenes (dissolved in dimethyl sulfoxide and in distilled water, FDS). After high-frequency electrical stimulation of the triceps surae muscle, the main fatigue-related increases in the c-Fos expression level were registered ipsilaterally within lamina 1 and 5 of the lumbar segments and within the contralateral capsular part of the CeA. C60 fullerene pretreatment in animals with subsequent electrical stimulation induced a distinct (2-4 times) decrease in the level of Fos immunoreactivity in the observed structures in comparison with only fatigue-induced rats. It can be supposed that FDS, as antioxidant compound, can decrease the concentration of free radicals in fatigued tissue and reduce the transmission intensity of nociceptive information from muscles to the spinal cord and amygdala, thereby changing the level of c-Fos expression within the lumbar segments and CeA.


Asunto(s)
Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Fulerenos/farmacología , Fatiga Muscular/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Amígdala del Cerebelo/fisiología , Animales , Antioxidantes/metabolismo , Fenómenos Electrofisiológicos/efectos de los fármacos , Fulerenos/química , Masculino , Ratas , Ratas Wistar , Médula Espinal/fisiología
15.
Bioorg Chem ; 96: 103568, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31972464

RESUMEN

Betulin is a natural pentacyclic triterpenoid, possessing a lupane-structure, with a wide range of pharmacological activities. Its weak hydrosolubility hinders the biological activity of the compound and its derivatives. To circumvent this problem, we synthesized and tested in vitro three d-glycosaminosides of betulin. The structure of betulin was modified by incorporation of 2-amino-2-deoxy-d-gluco- and -d-galactopyranosyl moieties to its C-3 position. So far betulinyl glycosides containing these amino-sugars have not been reported in the literature. The structure of the studied derivatives was confirmed by 1H and 13C NMR spectroscopy as well as mass spectrometry. The 28-O-acetylbetulin-3-yl 2-amino-2-deoxy-ß-d-glucopyranoside and betulin-3-yl 2-amino-2-deoxy-ß-d-gluco- and ß-d-galactopyranoside were tested against the human pathogenic fungi and Gram-positive and Gram-negative bacteria. Moreover, the MTT assay of their cytotoxicity was performed on the MCF-7 breast cancer cell line and on the HDFa, human dermal fibroblasts. The Ames test on mutagenic properties completed our biological assays.


Asunto(s)
Diseño de Fármacos , Glicósidos/química , Glicósidos/farmacología , Piranos/química , Triterpenos/química , Antibacterianos/farmacología , Antineoplásicos/farmacología , Pruebas de Carcinogenicidad , Ensayos de Selección de Medicamentos Antitumorales , Fibroblastos/efectos de los fármacos , Glicósidos/síntesis química , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Células MCF-7 , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Pruebas de Mutagenicidad , Piel/citología , Piel/efectos de los fármacos
16.
Nanomaterials (Basel) ; 9(7)2019 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-31277307

RESUMEN

Among metal-based nanoparticles, silver nanoparticles (AgNPs) are particularly appealing because of their stability, functionality, and documented antimicrobial properties. AgNPs also offer the possibility of different surface modifications. In this work, we functionalized AgNPs with thiobarbituric acid or 11-mercaptoundecanoic acid residues to improve the nanoparticles' biological activities. Subsequently, we assessed the physicochemical properties of newly synthesized AgNPs using a wide range of biophysical methodologies, including UV/vis and fluorescence spectroscopy, atomic force and scanning electron microscopy, and dynamic light scattering and isothermal titration calorimetry. Next, we examined the effect of nanoparticles functionalization on AgNPs mutagenicity and toxicity. Our study revealed that AgNPs' surface modification affects nanoparticles aggregation, and also impacts nanoparticles' interaction with model acridine mutagen ICR-191. AgNPs coated with MUA showed the most interesting interactions with tested ICR-191, slightly modulating its toxicity properties by decreasing the viability in treated cells.

17.
Sci Rep ; 9(1): 4987, 2019 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-30899037

RESUMEN

One of the greatest challenges of modern medicine is to find cheaper and easier ways to produce transporters for biologically active substances, which will provide selective and efficient drug delivery to the target cells, while causing low toxicity towards healthy cells. Currently, metal-based nanoparticles are considered a successful and viable solution to this problem. In this work, we propose the use of novel synthesis method of platinum nanoparticles (PtNPs) connected with their precise biophysical characterization and assessment of their potential toxicity. To work as an efficient nanodelivery platform, nanoparticles should interact with the desired active compounds spontaneously and non-covalently. We investigated possible direct interactions of PtNPs with ICR-191, a model acridine mutagen with well-established biophysical properties and mutagenic activity, by Dynamic Light Scattering, fluorescence spectroscopy, and Isothermal Titration Calorimetry. Moreover, to determine the biological activity of ICR-191-PtNPs aggregates, we employed Ames mutagenicity test, eukaryotic cell line analysis and toxicity test against the model organism Caenorhabditis elegans. PtNPs' interesting physicochemical properties associated to the lack of toxicity in a tested range of concentrations, as well as their ability to modulate ICR-191 biological activity, suggest that these particles successfully work as potential delivery platforms for different biologically active substances.


Asunto(s)
Aminacrina/análogos & derivados , Sistemas de Liberación de Medicamentos/efectos adversos , Nanopartículas del Metal/química , Compuestos de Mostaza Nitrogenada/química , Platino (Metal)/química , Aminacrina/síntesis química , Aminacrina/química , Aminacrina/uso terapéutico , Fenómenos Biofísicos , Humanos , Nanopartículas del Metal/uso terapéutico , Mutágenos/química , Mutágenos/uso terapéutico , Mutágenos/toxicidad , Compuestos de Mostaza Nitrogenada/síntesis química , Compuestos de Mostaza Nitrogenada/uso terapéutico
18.
Curr Pharm Biotechnol ; 19(3): 206-216, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29804530

RESUMEN

BACKGROUND: Pentoxifylline (PTX) is a drug commonly used in the treatment of intermittent claudication. However, numerous research groups report that PTX also may potentially be used in the anticancer therapy following one of the main trends in the nowadays medicine - combined anticancer therapy. SCOPE OF REVIEW: The review concentrates on the reports revealing the potential use of PTX in cancer treatment. Major Conclusion: PTX is described to possess several properties which may be exploited in cancer treatment. The drug reportedly not only has anticancer activity itself, but also increases cancer cells susceptibility to radiation therapy and, additionally, reduces long-term side effects of this therapy. Furthermore, numerous research groups report that PTX may increase the anticancer potential of commonly used anticancer drugs such as cisplatin or doxorubicin as well as reduce side effects of these drugs. SIGNIFICANCE: PTX should be considered as a potential drug in the combined anticancer therapy.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Pentoxifilina/uso terapéutico , Animales , Humanos
19.
Colloids Surf B Biointerfaces ; 164: 134-143, 2018 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-29413590

RESUMEN

C60 fullerene is reported to directly interact with biomolecules, such as aromatic mutagens or anticancer drugs. Therefore, it is extensively studied for its potential application in the fields of drug delivery and chemoprevention. Understanding the nature of fullerene-drugs interactions might contribute to optimization and modification of the existing chemotherapy systems. Possible interactions between ICR-191, a model acridine mutagen, with well-established biophysical properties and mutagenic activity, and C60 fullerene aqueous solution were investigated by broad range of biophysical methods, such as Dynamic Light Scattering, Isothermal Titration Calorimetry, and Atomic Force Microscopy. Additionally, to determine biological activity of ICR-191-C60 fullerene mixtures, Ames mutagenicity test was employed. It was demonstrated that C60 fullerene interacts non-covalently with ICR-191 and has strong affinity to bacterial membranes. The obtained results provide practical insight into C60 fullerene interactions with aromatic compounds.


Asunto(s)
Fulerenos/química , Hidrocarburos Aromáticos/metabolismo , Aminacrina/análogos & derivados , Aminacrina/metabolismo , Transporte Biológico , Fenómenos Biofísicos , Microscopía de Fuerza Atómica , Modelos Moleculares , Mutágenos/toxicidad , Compuestos de Mostaza Nitrogenada/metabolismo , Salmonella typhimurium/efectos de los fármacos
20.
Beilstein J Org Chem ; 12: 1434-9, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27559394

RESUMEN

This paper presents a study on a series of quaternary ammonium salt (QAS) derivatives of glucopyranosides with an elongated hydrophobic hydrocarbon chain. The new N-[6-(ß-D-glucopyranosyloxy)hexyl]ammonium bromides and their O-acetyl derivatives were analyzed via (1)H and (13)C NMR spectroscopy. The mutagenic activity of the newly synthesized QAS was investigated using two different techniques: The Vibrio harveyi luminescence assay and the Ames test. The obtained results support previous findings contesting QAS safety and indicate that QAS, specifically pyridinium derivatives, might be mutagenic.

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