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61.
Selective Cytotoxicity of 1,3,4-Thiadiazolium Mesoionic Derivatives on Hepatocarcinoma Cells (HepG2)
Gustavo Jabor Gozzi Amanda do Rocio Andrade Pires Glaucio Valdameri Maria Eliane Merlin Rocha Glaucia Regina Martinez Guilhermina Rodrigues Noleto Alexandra Acco Carlos Eduardo Alves de Souza Aurea Echevarria Camilla Moretto dos Reis Attilio Di Pietro Sílvia Maria Suter Correia Cadena 《PloS one》2015,10(6)
In this work, we evaluated the cytotoxicity of mesoionic 4-phenyl-5-(2-Y, 4-X or 4-X-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride derivatives (MI-J: X=OH, Y=H; MI-D: X=NO2, Y=H; MI-4F: X=F, Y=H; MI-2,4diF: X=Y=F) on human hepatocellular carcinoma (HepG2), and non-tumor cells (rat hepatocytes) for comparison. MI-J, M-4F and MI-2,4diF reduced HepG2 viability by ~ 50% at 25 μM after 24-h treatment, whereas MI-D required a 50 μM concentration, as shown by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. The cytotoxicity was confirmed with lactate dehydrogenase assay, of which activity was increased by 55, 24 and 16% for MI-J, MI-4F and MI-2,4diF respectively (at 25 μM after 24 h). To identify the death pathway related to cytotoxicity, the HepG2 cells treated by mesoionic compounds were labeled with both annexin V and PI, and analyzed by flow cytometry. All compounds increased the number of doubly-stained cells at 25 μM after 24 h: by 76% for MI-J, 25% for MI-4F and MI-2,4diF, and 11% for MI-D. It was also verified that increased DNA fragmentation occurred upon MI-J, MI-4F and MI-2,4diF treatments (by 12%, 9% and 8%, respectively, at 25 μM after 24 h). These compounds were only weakly, or not at all, transported by the main multidrug transporters, P-glycoprotein, ABCG2 and MRP1, and were able to slightly inhibit their drug-transport activity. It may be concluded that 1,3,4-thiadiazolium compounds, especially the hydroxy derivative MI-J, constitute promising candidates for future investigations on in-vivo treatment of hepatocellular carcinoma. 相似文献
62.
Silvia Del Ry Daniela Giannessi Maristella Maltinti Manuela Cabiati Concetta Prontera Annalisa Iervasi Chiara Caselli Anna Maria Mazzone Danilo Neglia 《Cytokine》2010,49(3):325-330
In patients with dilated cardiomyopathy (DCM) abnormal myocardial blood flow (MBF) has been associated with coronary microvascular dysfunction. The aim of this study was to test the hypothesis that osteopontin (OPN) plasma levels could be associated with the activation of the renin–aldosterone system (RAS) in these patients and be involved in mediating myocardial and coronary damage. In 66 patients with idiopathic left ventricular dysfunction of variable severity the plasma levels of OPN were correlated with biomarkers of systemic metabolism, RAS activation, myocardial dysfunction and with clinical indexes of left ventricle (LV) function and perfusion obtained by 2D-echocardiography and PET. As compared to controls, patients showed a significant increase of inflammatory markers (OPN: 508 ± 30.8 ng/ml vs. 426.9 ± 16.4, p < 0.05 and interleukin (IL)-6: 1.71 ± 0.29 pg/ml vs. 0.38 ± 0.03 pg/ml, p < 0.001) and of indexes of cardiac damage. OPN levels were significantly correlated with the extent of microvascular dysfunction (MBF at rest: p = 0.01; during dipyridamole: p = 0.0003) and with plasma renin activity (PRA) (r = 0.26, p = 0.04). Both in patients with milder or more severe LV dysfunction lower MBF values were associated with higher OPN levels and PRA. These results suggest a interdependent role of RAS and vascular inflammation in cardiomyopathy. 相似文献
63.
Figura N Franceschi F Santucci A Bernardini G Gasbarrini G Gasbarrini A 《Helicobacter》2010,15(Z1):60-68
The possible role of Helicobacter pylori as a trigger for some extragastric diseases has been largely investigated in the last year. There are, in fact, several studies concerning cardiovascular diseases, neurological disorders, diabetes mellitus, ear and eyes diseases, immunological and hematological disorders, liver and bile tract diseases, gynecological and respiratory tract pathologies. Among them, idiopathic sideropenic anemia and idiopathic thrombocytopenic purpura still remain the extragastric diseases showing the most convincing results. Concerning ischemic heart disease, there are new interesting data playing in favor of the association, even though there are still some open issues to be clarified. For the other diseases, more studies are needed to clarify the reality of the proposed association. 相似文献
64.
The Dof protein DAG1 mediates PIL5 activity on seed germination by negatively regulating GA biosynthetic gene AtGA3ox1 总被引:2,自引:0,他引:2
65.
Malerich JP Lam JS Hart B Fine RM Klebansky B Tanga MJ D'Andrea A 《Bioorganic & medicinal chemistry letters》2010,20(24):7454-7457
Tyrosine kinase 2 (TYK2) is required for signaling of interleukin-23 (IL-23), which plays a key role in rheumatoid arthritis. Presented is the design and synthesis of 1,2,4-triazoles, and the evaluation of their inhibitory activity against the Janus associated kinases TYK2 and JAKs 1-3. 相似文献
66.
Micheli F Antolini M Di Fabio R Pellacani A Pozzan A 《Bioorganic & medicinal chemistry letters》2010,20(22):6405-6407
A new class of selective orexin 2 antagonist was identified among commercial products. Initial SAR was obtained using commercial derivatives only prior to starting ad hoc medicinal chemistry activities. 相似文献
67.
68.
Francesca Froldi Marcello Ziosi Flavio Garoia Andrea Pession Nicola A Grzeschik Paola Bellosta Dennis Strand Helena E Richardson Annalisa Pession Daniela Grifoni 《BMC biology》2010,8(1):33
Background
Neoplastic overgrowth depends on the cooperation of several mutations ultimately leading to major rearrangements in cellular behaviour. Precancerous cells are often removed by cell death from normal tissues in the early steps of the tumourigenic process, but the molecules responsible for such a fundamental safeguard process remain in part elusive. With the aim to investigate the molecular crosstalk occurring between precancerous and normal cells in vivo, we took advantage of the clonal analysis methods that are available in Drosophila for studying the phenotypes due to lethal giant larvae (lgl) neoplastic mutation induced in different backgrounds and tissues. 相似文献69.
70.
D'Antona G Ragni M Cardile A Tedesco L Dossena M Bruttini F Caliaro F Corsetti G Bottinelli R Carruba MO Valerio A Nisoli E 《Cell metabolism》2010,12(4):362-372
Recent evidence points to a strong relationship between increased mitochondrial biogenesis and increased survival in eukaryotes. Branched-chain amino acids (BCAAs) have been shown to extend chronological life span in yeast. However, the role of these amino acids in mitochondrial biogenesis and longevity in mammals is unknown. Here, we show that a BCAA-enriched mixture (BCAAem) increased the average life span of mice. BCAAem supplementation increased mitochondrial biogenesis and sirtuin 1 expression in primary cardiac and skeletal myocytes and in cardiac and skeletal muscle, but not in adipose tissue and liver of middle-aged mice, and this was accompanied by enhanced physical endurance. Moreover, the reactive oxygen species (ROS) defense system genes were upregulated, and ROS production was reduced by BCAAem supplementation. All of the BCAAem-mediated effects were strongly attenuated in endothelial nitric oxide synthase null mutant mice. These data reveal an important antiaging role of BCAAs mediated by mitochondrial biogenesis in mammals. 相似文献