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71.
Cytotoxicity of new pyrazino[1,2-b]isoquinoline and 6,15-iminoisoquino[3,2-b]3-benzazocine compounds
Irene Ortín Juan Francisco González Elena de la Cuesta Carmen Avendaño 《Bioorganic & medicinal chemistry》2010,18(18):6813-6821
Looking for optimised analogues of compound 2 that might be useful in colon cancer therapy, we here explore the in vitro cytotoxicity against MDA-MB 231 human breast carcinoma, A-549 human lung carcinoma and HT-29 human colon carcinoma cell lines of several analogues and derivatives. The effect of the R2-substituent and/or the introduction of an arylmethyl side-chain at C-3, as well as the presence of a double bond in the skeleton or a methoxy group at C-1 have been investigated. New 6,15-iminoisoquino[3,2-b]3-benzazocine compounds, related to the saframycin family, in which the C(7)–N(8)–C(9)-substructure contains a lactam function, a fused oxazolidine or an aminonitrile function were also studied, and many of them showed low micromolar GI50 values. 相似文献
72.
73.
Díaz-Rosales P Salinas I Rodríguez A Cuesta A Chabrillón M Balebona MC Moriñigo MA Esteban MA Meseguer J 《Fish & shellfish immunology》2006,20(4):482-492
The effects of the dietary administration of two heat-inactivated whole bacteria from the Vibrionaceae family, singly or combined, on innate immune response of the seabream were studied. The two bacteria (Pdp11 and 51M6), which were obtained from the skin of gilthead seabream, showed in vitro characteristics that suggested they could be considered as potential fish probiotics. The fish were fed four different diets: control (non-supplemented), or diets supplemented with heat-inactivated bacteria at 10(8) cfu g(-1) Pdp11, 10(8) cfu g(-1) 51M6 or with 0.5 x 10(8) cfu g(-1) Pdp11 plus 0.5 x 10(8) cfu g(-1) 51M6 for 4 weeks. Six fish were sampled at weeks 1, 2, 3 and 4, when the main humoral (natural haemolytic complement activity and serum peroxidase content) and cellular innate immune responses (leucocyte peroxidase content, phagocytosis, respiratory burst and cytotoxicity) were evaluated. The serum peroxidase content and the natural haemolytic complement activity increased with time, reaching the highest values in the third and fourth weeks of feeding, respectively. The phagocytic ability of specimens fed the mixture of the two inactivated bacteria was significantly higher than in the controls after 2 and 3 weeks of treatment. The same activity increased significantly in seabream fed the Pdp11 diet for 2 weeks or the 51M6 diet for 3 weeks. Respiratory burst activity was unaffected by all the experimental diets at all times assayed. Cytotoxic activity had significantly increased after 3 weeks in fish fed the 51M6 diet. These results are discussed in terms of the usefulness of incorporating inactivated probiotic bacteria into fish diets. 相似文献
74.
Kinematical analysis of the snatch in elite male junior weightlifters of different weight categories
Campos J Poletaev P Cuesta A Pablos C Carratalá V 《Journal of strength and conditioning research / National Strength & Conditioning Association》2006,20(4):843-850
The purpose of this study was to analyze the differences in the technical pattern of the snatch in elite junior weightlifters of different weight categories. The sample was a group of 33 men weightlifters from different weight categories. The comparative study included 2 groups, taking into account weight categories. Group A included 17 weightlifters from the lightest categories, 56 and 62 kg; group B included 16 weightlifters from the heaviest categories, 85 and 105 kg. Three-dimensional photogrammetry technique was utilized. Regarding group differences, we can conclude that lifters belonging to heavier categories are more efficient, as they manage to have longer barbell propulsion trajectories, which allows them to exert actions on the barbell for a longer period, especially in the initial lifting phase. They attain greater barbell vertical velocity (p = 0.029), a longer vertical bar trajectory normalized on first pull (p = 0.011), and a greater, although limited, bar height loss on the catch (p = 0.008). Besides, intergroup differences evidence that heavier category lifters observe a different temporal organization of the movement based on a longer first pull (p = 0.000), a shorter transition (p = 0.030), and a longer turnover (p = 0.049). No significant differences were found in the analyzed angular parameters during the first and second pull. We believe the intergroup differences found not to be determining enough to consider a technical model adapted to the characteristics of each body weight category. This confirms that a successful lift is multifactor based and individual dependent. Given its transcendence, this evidence should be taken into account in the technical training of young lifters. 相似文献
75.
Dobrovolskaia MA Medvedev AE Thomas KE Cuesta N Toshchakov V Ren T Cody MJ Michalek SM Rice NR Vogel SN 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(1):508-519
In this study, tolerance induction by preexposure of murine macrophages to Toll-like receptor (TLR)2 and TLR4 agonists was revisited, focusing on the major signaling components associated with NF-kappaB activation. Pretreatment of macrophages with a pure TLR4 agonist (protein-free Escherichia coli (Ec) LPS) or with TLR2 agonists (Porphyromonas gingivalis LPS or synthetic lipoprotein Pam3Cys) led to suppression of TNF-alpha secretion, IL-1R-associated kinase-1, and IkappaB kinase (IKK) kinase activities, c-jun N-terminal kinase, and extracellular signal-regulated kinase phosphorylation, and to suppression of NF-kappaB DNA binding and transactivation upon challenge with the same agonist (TLR4 or TLR2 "homotolerance," respectively). Despite inhibited NF-kappaB DNA binding, increased levels of nuclear NF-kappaB were detected in agonist-pretreated macrophages. For all the intermediate signaling elements, heterotolerance was weaker than TLR4 or TLR2 homotolerance with the exception of IKK kinase activity. IKK kinase activity was unperturbed in heterotolerance. TNF-alpha secretion was also suppressed in P. gingivalis LPS-pretreated, Ec LPS-challenged cells, but not vice versa, while Pam3Cys and Ec LPS did not induce a state of cross-tolerance at the level of TNF-alpha. Experiments designed to elucidate novel mechanisms of NF-kappaB inhibition in tolerized cells revealed the potential contribution of IkappaBepsilon and IkappaBxi inhibitory proteins and the necessity of TLR4 engagement for induction of tolerance to Toll receptor-IL-1R domain-containing adapter protein/MyD88-adapter-like-dependent gene expression. Collectively, these data demonstrate that induction of homotolerance affects a broader spectrum of signaling components than in heterotolerance, with selective modulation of specific elements within the NF-kappaB signaling pathway. 相似文献
76.
77.
J P De La Cruz L Quintero J Galvez M A Villalobos F Sánchez de la Cuesta 《Life sciences》1999,65(5):543-555
The dietary intake of saturated fatty acids affects arteriosclerosis. We studied the effect of supplementation (15% wt/wt) of a hyperlipemic diet (1.33% cholesterol) with evening primrose oil (EPO) (Oenothera biennis) for 6 weeks in four groups of 10 rabbits each. At the end of this period we determined lipid peroxidation, glutathione content, and glutathione peroxidase, reductase and transferase activities in liver, brain, heart, aorta and platelets. The atherogenic diet increased tissue lipid peroxidation and decreased the protective antioxidant effect of glutathione. Dietary supplementation with EPO reduced tissue lipid peroxidation (61% in liver, 57% in brain, 42% in heart, 24% in aorta, 33% in platelets). Total glutathione was increased, especially in the aorta (90%) and platelets (200%); however, in all tissues the percentage of oxidised glutathione decreased. Evening primrose oil reduced glutathione peroxidase activity and increased the activities of glutathione reductase and transferase. We conclude that in rabbits made hyperlipemic with a diet rich in saturated fatty acids, EPO decreased tissue oxidative stress. 相似文献
78.
Magyar A Wölfling J Kubas M Cuesta Seijo JA Sevvana M Herbst-Irmer R Forgó P Schneider G 《Steroids》2004,69(5):301-312
Steroidal aryliminium salts were prepared from D-seco-pregnene aldehyde 2b, and their BF3.OEt2-catalyzed reactions were studied. The nature of the substituent R1 in the anilines 3-6 essentially influenced the chemoselectivity. Using unsubstituted 3, 4-methoxy- (4) or 4-bromoaniline (5), different tetrahydroquinoline derivatives 7a-13a via intramolecular hetero Diels-Alder reaction were formed. In the case of 4-nitroaniline (6) the N-arylamino-D-homopregnane (14a) were also obtained. We assume, that an intramolecular Prins reaction led to this type of fluoro-D-homosteroid. The main products represent a new class of tetrahydroquinolino-androstenes. 相似文献
79.
Structural basis for competitive inhibition of eIF4G-Mnk1 interaction by the adenovirus 100-kilodalton protein
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Translation of most cellular mRNAs involves cap binding by the translation initiation complex. Among this complex of proteins are cap-binding protein eIF4E and the eIF4E kinase Mnk1. Cap-dependent mRNA translation generally correlates with Mnk1 phosphorylation of eIF4E when both are bound to eIF4G. During the late phase of adenovirus (Ad) infection translation of cellular mRNA is inhibited, which correlates with displacement of Mnk1 from eIF4G by the viral 100-kDa (100K) protein and dephosphorylation of eIF4E. Here we describe the molecular mechanism for 100K protein displacement of Mnk1 from eIF4G and elucidate a structural basis for eIF4G interaction with Mnk1 and 100K proteins and Ad inhibition of cellular protein synthesis. The eIF4G-binding site is located in an N-terminal 66-amino-acid peptide of 100K which is sufficient to bind eIF4G, displace Mnk1, block eIF4E phosphorylation, and inhibit eIF4F (cap)-dependent cellular mRNA translation. Ad 100K and Mnk1 proteins possess a common eIF4G-binding motif, but 100K protein binds more strongly to eIF4G than does Mnk1. Unlike Mnk1, for which binding to eIF4G is RNA dependent, competitive binding by 100K protein is RNA independent. These data support a model whereby 100K protein blocks cellular protein synthesis by coopting eIF4G and cap-initiation complexes regardless of their association with mRNA and displacing or blocking binding by Mnk1, which occurs only on preassembled complexes, resulting in dephosphorylation of eIF4E. 相似文献
80.
Structural phosphoprotein M2-1 of the human respiratory syncytial virus is an RNA binding protein
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The structural phosphoprotein M2-1 of human respiratory syncytial virus (HRSV) Long strain shows RNA binding capacity in three different assays that detect RNA-protein complexes: cross-linking, gel retardation, and Northern-Western assays. It is able to bind HRSV leader RNA specifically with cooperative kinetics, with an apparent K(d) of at least 90 nM. It also binds to long RNAs with no sequence specificity. The RNA binding domain has been located between amino acid residues 59 and 85, at the NH(2) terminus of the protein. This region contains the phosphorylatable amino acid residues threonine 56 and serine 58, whose modification decreases the binding capacity of M2-1 protein to long RNAs. 相似文献