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1.
Sci Rep ; 11(1): 23626, 2021 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-34880294

RESUMEN

We show a method to control magnetic interfacial effects in multilayers with Dzyaloshinskii-Moriya interaction (DMI) using helium (He[Formula: see text]) ion irradiation. We report results from SQUID magnetometry, ferromagnetic resonance as well as Brillouin light scattering results on multilayers with DMI as a function of irradiation fluence to study the effect of irradiation on the magnetic properties of the multilayers. Our results show clear evidence of the He[Formula: see text] irradiation effects on the magnetic properties which is consistent with interface modification due to the effects of the He[Formula: see text] irradiation. This external degree of freedom offers promising perspectives to further improve the control of magnetic skyrmions in multilayers, that could push them towards integration in future technologies.

2.
Nat Prod Res ; 35(21): 3850-3858, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32223360

RESUMEN

A series of unexpected triterpenic C17-[5-methyl-1,3]-oxazoles along with targeted N-propargylamides was synthesized by an interaction of acid chlorides with propargylamine hydrochloride. We proposed that the formation of methyl oxazole passes through an alternative pathway by the participation of the terminal alkyne carbon atom and acid chloride intermediate with following intramolecular rearrangements. The synthesized compounds were evaluated for their cytotoxicity at the U.S. National Cancer Institute. 28-Nor-17-(5-methyloxazol-2-yl)-2-cyano-2,4-seco-3-nor-lup-4(23),20(29)-diene has demonstrated the highest activity with GI50 ranged from 1.03 to 16.4 µM against different cancer cell lines. Molecular docking in Kelch domain of Keap1 protein was performed to study a possible molecular target. Thus, we have shown for the first time that triterpenic C17-[5-methyl-1,3]-oxazoles are alternative products of the interaction of triterpenic acid chlorides with propargylamine hydrochloride and they have an advantage over corresponding N-propargylamides as cytotoxic agents.


Asunto(s)
Triterpenos , Proteína 1 Asociada A ECH Tipo Kelch , Simulación del Acoplamiento Molecular , Factor 2 Relacionado con NF-E2 , Oxazoles , Triterpenos/farmacología
3.
Khirurgiia (Mosk) ; (11): 5-13, 2020.
Artículo en Ruso | MEDLINE | ID: mdl-33210501

RESUMEN

OBJECTIVE: To improve the outcomes in children with hepatoblastoma. MATERIAL AND METHODS: There were 160 children with focal liver lesions who underwent surgery at the department of liver transplantation in 2008-2019. Patients with malignant tumors made up 77% (n=123). Hepatoblastoma (HB) prevailed (86%, n=106). Liver transplantation was performed in 19 (18%) patients with HB. Median follow-up after transplantation was 24.3 months by December 2019. Follow-up period did not exceed 4 years in more than 2/3 of patients. RESULTS: Overall and disease-free 10-year survival was 87.1% and 82.7%, respectively. Similar values were observed after resections (91.1% and 86.6%). At the same time, actuarial 4-year survival after liver transplantation for HB was 68%. CONCLUSION: Improvement of treatment outcomes may be achieved through multidisciplinary interaction ensuring timely drug therapy and liver transplantation.


Asunto(s)
Hepatoblastoma , Neoplasias Hepáticas , Trasplante de Hígado , Niño , Terapia Combinada , Hepatectomía , Hepatoblastoma/cirugía , Humanos , Lactante , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
4.
Int J Cosmet Sci ; 42(5): 429-435, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32485024

RESUMEN

OBJECTIVE: Microneedle patches based on dissolving, detachable microneedle technology (Russian patent No. 2652567; US patent EFS No. 32735812; WO/2019/231360) are novel dermatological products that allow safe, painless and effective reduction of epidermal wrinkles after six procedures. The purpose of this study was two-fold (a) to assess the safety and efficacy of microneedle patches comprising 650 microneedles containing hyaluronic and ferulic acids after 6 procedures of applying the applicator to the skin for 25 min; and (b) to correlate our previously reported ex vivo findings. METHODS: The microneedle applicator contains 650 microneedles, which dissolve in 25 min of exposure. The effectiveness of microneedle applicators was confirmed by a randomized split-phase study involving 82 subjects. Applications of microneedle patches were performed at intervals of two times per week, and the effectiveness was assessed at 6 weeks after the start of the study. RESULTS: The results of the profilometric evaluation of skin smoothness demonstrated a significant reduction in the average roughness index by 65.32 ± 2.99% and in the mean skin waviness by 66.84 ± 1.6% compared with these indicators in the control group (P < 0.05). The therapeutic effect of the procedure was confirmed by an ultrasound examination that registered a 72.2 ± 5.4% and 25 ± 1.4% increase in echo-density of the epidermis and dermis, respectively. An independent blinded skin evaluation by dermatologists revealed steady decrease in puffiness of the application area in 89.9% of patients, increased elasticity in 78.3% of the patients, and reduced severity of epidermal wrinkles in 89.9% of the patients. CONCLUSIONS: The applicator with 650 soluble microneedles on its surface containing hyaluronic and ferulic acids is considered a safe, effective and convenient way to improve the skin quality in the periorbital region after six procedures. Nevertheless, additional studies of soluble microneedles are required to fully assess the amount and distribution area of the injected hyaluronic acid and other active components, as well as to detail the mechanism of action of soluble microneedles to improve skin quality.


OBJECTIF: Les patchs Microneedle basés sur la technologie de micro-aiguille dissolvante et détachable (brevet russe n ° 2652567; brevet américain EFS n ° 32735812; WO / 2019/231360) sont de nouveaux produits dermatologiques qui permettent une réduction sûre, indolore et efficace des rides épidermiques après 6 procédures. Le but de cette étude était double: a) évaluer l'innocuité et l'efficacité des patchs de micro-aiguilles comprenant 650 micro-aiguilles contenant des acides hyaluronique et férulique après 6 procédures d'application de l'applicateur sur la peau pendant 25 minutes; et b) pour corréler nos résultats ex-vivo précédemment rapportés. MÉTHODES: L'applicateur de micro-aiguilles contient 650 micro-aiguilles, qui se dissolvent en 25 minutes d'exposition. L'efficacité des applicateurs de micro-aiguilles a été confirmée par une étude randomisée en hémi-visage portant sur 82 sujets. Des applications de patchs de micro-aiguilles ont été effectuées à des intervalles de 2 fois par semaine, et l'efficacité a été évaluée 6 semaines après le début de l'étude. RÉSULTATS: Les résultats de l'évaluation profilométrique de la douceur de la peau ont démontré une réduction significative de l'indice de rugosité moyen de 65,32 ± 2,99% et de l'ondulation cutanée moyenne de 66,84 ± 1,6% par rapport à ces indicateurs dans le groupe témoin (p <0,05). L'effet thérapeutique de la procédure a été confirmé par un examen échographique qui a enregistré une augmentation de 72,2 ± 5,4% et 25 ± 1,4% de l'écho-densité de l'épiderme et du derme, respectivement. Une évaluation indépendante de la peau en aveugle par des dermatologues a révélé une diminution constante des poches de la zone d'application chez 89,9% des patients, une augmentation de l'élasticité chez 78,3% des patients et une réduction de la gravité des rides épidermiques chez 89,9% des patients. CONCLUSIONS: L'applicateur avec 650 micro-aiguilles solubles à sa surface contenant des acides hyaluronique et férulique est considéré comme un moyen sûr, efficace et pratique d'améliorer la qualité de la peau dans la région périorbitaire après 6 procédures. Néanmoins, des études supplémentaires sur les micro-aiguilles solubles sont nécessaires pour évaluer pleinement la quantité et la zone de distribution de l'acide hyaluronique injecté et d'autres composants actifs, ainsi que pour détailler le mécanisme d'action des micro-aiguilles solubles pour améliorer la qualité de la peau.


Asunto(s)
Agujas , Órbita , Envejecimiento de la Piel/efectos de los fármacos , Piel , Parche Transdérmico , Adulto , Ácidos Cumáricos/administración & dosificación , Ácidos Cumáricos/farmacología , Sistemas de Liberación de Medicamentos/métodos , Cara , Femenino , Humanos , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/farmacología , Persona de Mediana Edad , Solubilidad
5.
Vavilovskii Zhurnal Genet Selektsii ; 24(2): 139-148, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33659793

RESUMEN

The Septoria blotch of spring wheat leaves and ears is one of the most economically significant infections in the Siberian region. In the control systems of Septoria blotch the main ecologically safe element is resistant varieties, which are designed to slow down the pathogens reproduction rate and slow down or stop the development of the epiphytotic process. The purpose of the work was to clarify the species composition of Septoria blotch pathogens for West Siberian regions and spring wheat varieties, to study the epiphytotic process of Septoria differentially on the leaves and ears of varieties, and to evaluate the activity of seed transmission of Parastagonospora nodorum. Studies were carried out in 2016-2018 according to generally accepted methods. Septoria leaf and ear blotch of spring wheat is widespread in West Siberia and the Trans-Urals, causing a decrease in yield by up to 50 % or more with the deterioration in grain quality. The causative agents of the disease are P. nodorum, Septoria tritici, and P. avenae f. sp. triticae, and the species ratio varied across the regions and varieties, and within plant organs. In Novosibirsk Region, P. nodorum completely dominated; S. tritici was 13.8 times less common; and P. avenae f. sp. triticae was a singleton. In Tyumen Region, the dominance of P. nodorum was disrupted in some geographic locations by S. tritici and P. avenae f. sp. triticae. In Altai Krai, P. nodorum predominated at all points studied; S. tritici and P. avenae f. sp. triticae were found everywhere, but 5.6 and 8.6 times less often, respectively. The study of spring wheat varieties of different origins has not revealed any samples immune to Septoria blotch. A differentiated manifestation of resistance to Septoria leaf and ear disease has been established. Some varieties show complex resistance, combining reduced susceptibility to Septoria leaf and ear disease. Seed infection with P. nodorum in the regions of Siberia reached 7 thresholds and was largely (52.5 %) determined by the August weather conditions. The study of the collection of spring wheat varieties from three Siberian regions has revealed the following trend. Transmission of P. nodorum with the seeds of varieties was the most active (7.6 %) in Novosibirsk Region and somewhat weaker in Omsk Region (5.7 %). The most favorable phytosanitary situation was in Kurgan Region, where varieties transmitted P. nodorum to a low degree (2.1 %), below the threshold.

6.
Biochemistry (Mosc) ; 84(1): 11-19, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30927521

RESUMEN

Myosin II is the main molecular motor in the actomyosin-dependent motility in cells. Phosphorylation of the myosin regulatory light chain (RLC) at Ser19 is a prerequisite for smooth muscle/non-muscle myosin II activation and serves as a biochemical equivalent of myosin II activity. Simultaneous phosphorylation at Thr18 further promotes the myosin II ATPase activity. A number of methods have been developed to measure myosin RLC phosphorylation at Ser19 or di-phosphorylation at Thr18/Ser19. While these methods are straightforward and robust in myosin-rich muscle tissues, they demonstrate limited applicability in non-muscle cells that have low myosin II content and are usually available in lesser amounts than muscle tissue. Because of this, dynamic analysis of RLC phosphorylation in multiple samples of non-muscle cells is difficult and requires large number of cells. The use of phospho-specific antibodies increases detection sensitivity but allows estimation of only relative levels of RLC phosphorylation at specific residues, which makes it difficult to estimate the physiologic relevancy of the observed changes in RLC phosphorylation. To measure RLC phosphorylation in small amounts of non-muscle cells, we used external calibration standards of non-phosphorylated and in vitro phosphorylated RLC in standard SDS-PAGE and Western blot procedures with phospho-specific RLC antibodies. Here, we describe the method in detail and demonstrate its application for quantitative measurement of myosin RLC phosphorylation in endothelial cells in response to natural agonists (thrombin or insulin) and intact human platelets. We discuss the advantages and limitations of the proposed method vs other approaches for measuring myosin RLC phosphorylation in non-muscle cells.


Asunto(s)
Western Blotting/métodos , Cadenas Ligeras de Miosina/metabolismo , Fosforilación , Plaquetas , Electroforesis en Gel de Poliacrilamida/métodos , Células Endoteliales/metabolismo , Humanos , Insulina/farmacología , Trombina/farmacología
7.
Bull Exp Biol Med ; 164(6): 753-756, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29658078

RESUMEN

We studied the role of the carrier status for polymorphic loci of genes encoding estrogen receptors (ESR1), endothelial NO synthase (eNOS), and apolipoprotein E (APOE4) and products of their expression nitrogen oxide (NO) and apolipoprotein (ApoE) in the development of arterial hypertension in men. Conventionally healthy volunteers and 149 men with clinical manifestations of stage I-II arterial hypertension were examined. In men with arterial hypertension, the frequency of minor allele A of ESR1 gene was higher (27.5 vs. 9.5% in the reference group; χ2=4.43, p=0.04). The level of NO in the peripheral blood was also higher in the main group (χ2=3.93, p=0.047). The increase in NO concentration did not depend on the presence of polymorphic genotypes (GG and GT) of eNOS gene, but the decrease in ApoE level in blood serum was associated with TC genotype of APOE4 gene (p=0.04). Our results suggest that minor allele A of ESR1 gene is associated with the development of arterial hypertension in men. Reduced content of ApoE in blood serum of men with arterial hypertension was associated with APOE4 gene polymorphism. However, increased level of NO did not depend on polymorphic genotypes GG and GT of eNOS gene. These polymorphisms are of specific interest as additional markers of genetic predisposition to the development of arterial hypertension in middle-age men.


Asunto(s)
Apolipoproteína E4/genética , Receptor alfa de Estrógeno/genética , Predisposición Genética a la Enfermedad , Hipertensión/genética , Óxido Nítrico Sintasa de Tipo III/genética , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Apolipoproteína E4/sangre , Estudios de Casos y Controles , Receptor alfa de Estrógeno/sangre , Expresión Génica , Frecuencia de los Genes , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo III/sangre , Óxidos de Nitrógeno/metabolismo , Índice de Severidad de la Enfermedad
8.
Nanoscale ; 9(10): 3440-3448, 2017 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-28232984

RESUMEN

The effects of humidity on the electronic properties of quasi-free standing one layer graphene (QFS 1LG) are investigated via simultaneous magneto-transport in the van der Pauw geometry and local work function measurements in a controlled environment. QFS 1LG on 4H-SiC(0001) is obtained by hydrogen intercalation of the interfacial layer. In this system, the carrier concentration experiences a two-fold increase in sensitivity to changes in relative humidity as compared to the as-grown epitaxial graphene. This enhanced sensitivity to water is attributed to the lowering of the hydrophobicity of QFS 1LG, which results from spontaneous polarization of 4H-SiC(0001) strongly influencing the graphene. Moreover, the superior carrier mobility of the QFS 1LG system is retained even at the highest humidity. The work function maps constructed from Kelvin probe force microscopy also revealed higher sensitivity to water for 1LG compared to 2LG in both QFS 1LG and as-grown systems. These results point to a new field of applications for QFS 1LG, i.e., as humidity sensors, and the corresponding need for metrology in calibration of graphene-based sensors and devices.

10.
Bioorg Khim ; 41(3): 346-56, 2015.
Artículo en Ruso | MEDLINE | ID: mdl-26502611

RESUMEN

Synthesis of lupane C28-imidazolides, contained 3-oxo-, 3-oximino- and 2-cyano-2,3-seco-4(23)-en-frag ments in cycle A was carried out. The most antitumor activity at. in vitro testing showed 3-oximino-lup- 20(29)-en-28-yl-1H-imidazole-1-carboxylate; which inhibited the growth or induced apoptosis of non-small lung cancer, colon cancer, breast cancer, CNS cancer, ovarian cancer, prostate cancer, leucosis, melanoma cells. In experiments in mice its moderate antitumor activity against grafted breast adenocarcinoma Ca 755 and adenocarcinima of colon was observed.


Asunto(s)
Antineoplásicos/síntesis química , Imidazoles/síntesis química , Ácido Oleanólico/análogos & derivados , Triterpenos/síntesis química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Femenino , Humanos , Imidazoles/administración & dosificación , Imidazoles/química , Masculino , Ratones , Ácido Oleanólico/administración & dosificación , Ácido Oleanólico/síntesis química , Ácido Oleanólico/química , Neoplasias de la Próstata/tratamiento farmacológico , Triterpenos/administración & dosificación , Triterpenos/química , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Bioorg Khim ; 40(2): 217-25, 2014.
Artículo en Ruso | MEDLINE | ID: mdl-25895342

RESUMEN

Synthesis of 3-deoxy-3a-homo-3a-aza-derivatives of betulin and erythrodiol from betulonic and oleanonic acids was carried out. The most antineoplastic activity with a wide range of action at in vitro testing showed 3-deoxy-3a-homo-3a-aza-28-hydroxy-12(13)-oleanene, which by results of profound studying could be recommended for in vivo investigation. Its modification in the C28 position by introduction of amethoxycinnamoyl fragment led to a loss of antineoplastic activity. 3-Deoxy-3a-homo-3a-aza-derivatives of betulin (3-(aminopropyl)-, 28-(2-carboxyethyl)carboxy-, and 28-cinnamoyloxy-) showed moderate antineoplastic activity in the case of Colon Cancer, Breast Cancer and Leukemia cell lines.


Asunto(s)
Neoplasias/tratamiento farmacológico , Ácido Oleanólico/análogos & derivados , Relación Estructura-Actividad , Triterpenos/síntesis química , Adamantano/síntesis química , Adamantano/química , Antineoplásicos/administración & dosificación , Antineoplásicos/síntesis química , Antineoplásicos/química , Antivirales/administración & dosificación , Antivirales/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias/patología , Ácido Oleanólico/síntesis química , Ácido Oleanólico/química , Triterpenos/química
12.
Bioorg Khim ; 40(5): 608-17, 2014.
Artículo en Ruso | MEDLINE | ID: mdl-25895356

RESUMEN

The synthesis and screening of antitumor activity in vitro (cytotoxicity) of various oxygen, nitrogen, sulfur and platinum-containing derivatives of allobetulin, including different arrangements of the double bonds in the A and B rings, penta- and hexacyclic ring A, 21-acetyl-20,28-epoxy-18α,19ßH-ursane-isomeric cycle E, was carry out. (3R,5R)-19ß,28-Epoxy-4,5-seco-18α-olean-3(5)-ozonide and 2,3-indolo-21ß-acetyl-20ß,28-epoxy-18α, H-19ß-ursane showed significant cytotoxic activity against melanoma MeWo and Leukemia SR cells, appropriately. (3S,5S)-Diastereomer of the first compound showed no cytotoxicity.


Asunto(s)
Triterpenos/química , Triterpenos/farmacología , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Estructura Molecular , Relación Estructura-Actividad , Triterpenos/síntesis química
13.
Lik Sprava ; (1): 22-9, 2013.
Artículo en Ucraniano | MEDLINE | ID: mdl-23951907

RESUMEN

Quantum pharmacology allows to study the mechanisms of action of cardiovascular drugs, to predict pharmacological activity and identify the most pronounced pharmacodynamic efficacy and therapeutic activity of new compounds. Calculation of quantum-pharmacological parameters for molecules of beta-blockers (propranolol, atenolol, metoprolol, carvedilol) in aqueous media, research its hydrophobic interaction with receptors allow to form a theoretical basis for the development of new generations of more effective and safe medicines for hypertension treatment. Increased hydrophobicity leads to poor solubility of carvedilol in water and high--in the lipids. The clinical pharmacology of the drug is shown by such indicators as the therapeutic dose, half-life and degree of metabolism in the liver. Due to enhanced interaction with adrenergic receptor effective dose of carvedilol is an order of magnitude lower than other beta-blockers, even with the relatively low bioavailability. Reduced bioavailability of carvedilol versus atenolol, metoprolol and propranolol is caused by elevated metabolism during the first pass through the liver, which is also due to the hydrophobicity of the drug. High solubility in lipids appears to extend the half-life of carvedilol. QSAR studies make an important contribution to the study of the properties of chemical compounds and their pharmacological activity. Software, used for computation of studied properties, has a significant role. A large number of descriptors allows a qualitative and quantitative assessment of the molecules of chemical compounds and prediction of their influence on cardiovascular system.


Asunto(s)
Fármacos Cardiovasculares , Descubrimiento de Drogas/métodos , Teoría Cuántica , Fármacos Cardiovasculares/química , Fármacos Cardiovasculares/farmacocinética , Fármacos Cardiovasculares/farmacología , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Relación Estructura-Actividad Cuantitativa , Solubilidad
14.
Bioorg Khim ; 39(2): 230-9, 2013.
Artículo en Ruso | MEDLINE | ID: mdl-23964524

RESUMEN

The synthesis and X-ray diffraction established the structure of (7R,8S)-(see text for symbol)-(13R,17R)-trioxolaneabietic acid. Predicted by the computer system PASS antineoplastic activity and the ability to induce apoptosis, a mechanism of cell death, is correlated with experimentally shown cytotoxic activity against malignant cell line MeWo. Results of tests on animals have shown that abietic acid and its 9R,11S-epoxy-12R,15R-trioxolane derivative have anti-inflammatory and antiulcer activity in the absence of adverse effects on animal organisms.


Asunto(s)
Abietanos/síntesis química , Abietanos/farmacología , Abietanos/química , Ácido Acético/toxicidad , Animales , Línea Celular Tumoral/efectos de los fármacos , Formaldehído/toxicidad , Humanos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Espectroscopía de Resonancia Magnética , Ratones , Ratas , Úlcera/inducido químicamente , Úlcera/tratamiento farmacológico , Úlcera/patología , Difracción de Rayos X
15.
Nanotechnology ; 24(21): 215702, 2013 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-23618748

RESUMEN

Surface potential distribution, V(CPD), and evolution of atmospheric adsorbates on few and multiple layers (FLG and MLG) of graphene grown on SiC(0001) substrate have been investigated by electrostatic and Kelvin force microscopy techniques at T = 20-120 °C. The change of the surface potential distribution, ΔV(CPD), between FLG and MLG is shown to be temperature dependent. The enhanced ΔV(CPD) value at 120 °C is associated with desorption of adsorbates at high temperatures and the corresponding change of the carrier balance. The nature of the adsorbates and their evolution with temperature are considered to be related to the process of adsorption and desorption of the atmospheric water on MLG domains. We demonstrate that both the nano- and microscale wettability of the material are strongly dependent on the number of graphene layers.


Asunto(s)
Atmósfera/química , Compuestos Inorgánicos de Carbono/química , Cristalización/métodos , Grafito/química , Microscopía Electrónica/métodos , Nanoestructuras/química , Nanoestructuras/ultraestructura , Compuestos de Silicona/química , Ensayo de Materiales , Conformación Molecular , Tamaño de la Partícula , Humectabilidad
16.
Bioorg Khim ; 39(3): 369-77, 2013.
Artículo en Ruso | MEDLINE | ID: mdl-24397036

RESUMEN

On the basis of betulinic and oleanolic acids triterpenoids with different with different amine fragments: (3-aminopropoxy)-, 3-acetyl-(3-aminopropyl)amino-, 6-[bis(3-aminopropyl)amino]hexylamino-, (3-aminopropyl)-4-aminosulfonyl-4-phenylamino- at positions C3 and C28 were synthesized. It is shown that betulonic acid amide with 4,4'-diaminodiphenylsulfonic substituent don't render antitumor effect in mice with transplantable Lewis lung carcinoma, but possess significant anti-inflammatory activity.


Asunto(s)
Ácido Oleanólico/administración & dosificación , Ácido Oleanólico/síntesis química , Triterpenos/síntesis química , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Antineoplásicos/administración & dosificación , Antineoplásicos/síntesis química , Antineoplásicos/química , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/patología , Histamina/toxicidad , Humanos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Ratones , Ácido Oleanólico/química , Triterpenos Pentacíclicos , Triterpenos/química
17.
Biofizika ; 57(5): 764-70, 2012.
Artículo en Ruso | MEDLINE | ID: mdl-23136768

RESUMEN

Novel peptides originating from the peptide inhibitor of myosin light chain kinase, L-PIK (Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys), have been studied for ability to attenuate the thrombin-induced hyperpermeability of endothelial cell monolayer in culture. Peptides [NalphaMeArg1]-Lys-Lys-Tyr-Lys-Tyr-Arg-(D)Arg8-Lys and H-Arg(NO2)Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys-NH2 (designated PIK2 and PIK4, respectively) appeared to be the most effective inhibitors of endothelial cell monolayer hyperpermebility, and surpassed other known peptide inhibitors of myosin light chain kinase derived from original L-PIK. Our results validate PIK2 and PIK4 as the leading molecules for the development of novel drugs intended to counteract pathological hyperpermeability of vascular endothelium.


Asunto(s)
Permeabilidad Capilar/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Quinasa de Cadena Ligera de Miosina/antagonistas & inhibidores , Péptidos/farmacología , Secuencia de Aminoácidos , Línea Celular , Cámaras de Difusión de Cultivos , Impedancia Eléctrica , Células Endoteliales/citología , Células Endoteliales/enzimología , Endotelio Vascular/citología , Endotelio Vascular/enzimología , Fluoresceína-5-Isotiocianato/análogos & derivados , Humanos , Cinética , Datos de Secuencia Molecular , Quinasa de Cadena Ligera de Miosina/metabolismo , Péptidos/síntesis química , Albúmina Sérica , Espectrometría de Fluorescencia , Relación Estructura-Actividad , Trombina/farmacología
18.
Lik Sprava ; (3-4): 3-13, 2012.
Artículo en Ucraniano | MEDLINE | ID: mdl-23356130

RESUMEN

The work is devoted to the use of quantum-pharmacological approaches in pharmacokinetic investigations. The main objective of the pharmacological researches is to find new, more active and less toxic drugs. To date, such a search is carried out empirically. The current approach can not fully meet the needs of medicine in the new drugs, requires considerable time and financial costs and does not meet modern standards of bioethics. Quantum pharmacology leads to the synthesis of drugs with desired properties is much faster and more efficient. Computer prediction of pharmacokinetic and biopharmaceutical properties of biologically active substances can make 50-70% more effective development of original drugs.


Asunto(s)
Simulación por Computador , Sistema Enzimático del Citocromo P-450/metabolismo , Diseño de Fármacos , Albúmina Sérica/química , Animales , Sitios de Unión , Sistema Enzimático del Citocromo P-450/química , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Modelos Químicos , Unión Proteica , Relación Estructura-Actividad Cuantitativa , Teoría Cuántica , Albúmina Sérica/metabolismo , Electricidad Estática , Termodinámica
19.
Bioorg Khim ; 37(3): 414-24, 2011.
Artículo en Ruso | MEDLINE | ID: mdl-21899058

RESUMEN

The synthesis of aminopropoxy derivatives of betulin, erythrodiol, uvaol and oleantriol via cyanoethylation of triterpenoids hydroxyl groups and subsequent reduction of cyanoethyl fragments is described. High and specific in vitro antitumor activity (cytotoxicity) of 3beta,28-di-O-[3-(aminopropoxy)]lupa-20(29)-ene and 3beta-O-hydroxy-28-O-[3-(aminopropoxy)]olean-12-ene towards a wide range of human tumor cell lines is discovered. The aminopropoxy group is shown to be a new perspective pharmacophor group for design of anticancer agents on the basis of triterpenoids.


Asunto(s)
Antineoplásicos/síntesis química , Ácido Oleanólico/análogos & derivados , Triterpenos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Humanos , Ácido Oleanólico/síntesis química , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , Triterpenos/química , Triterpenos/farmacología
20.
Bioorg Khim ; 37(5): 690-6, 2011.
Artículo en Ruso | MEDLINE | ID: mdl-22332366

RESUMEN

Development of the functionalization of triterpenoids to A-secoamidoximes, A-secomethylenamines and branched 3-(3-aminopropylamino)-3-(3-aminopropoxy)amidoximes is illustrated by the betulonic acid ketoxime. An effective way to get of the derivatives of 20,29-dihydrolupanes using diborane is suggested. The antiviral and anti-tuberculosis activity data of some compounds are presented.


Asunto(s)
Antituberculosos/síntesis química , Antivirales/síntesis química , Ácido Oleanólico/análogos & derivados , Oximas/síntesis química , Triterpenos/síntesis química , Antituberculosos/química , Antituberculosos/farmacología , Antivirales/química , Antivirales/farmacología , Humanos , Virus de la Influenza A/efectos de los fármacos , Estructura Molecular , Mycobacterium tuberculosis/efectos de los fármacos , Ácido Oleanólico/química , Oximas/química , Oximas/farmacología , Rhinovirus/efectos de los fármacos , Virus del SRAS/efectos de los fármacos , Relación Estructura-Actividad , Triterpenos/química , Triterpenos/farmacología
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