31 research outputs found

    4-(3-Fluoro­phen­yl)-1-(propan-2-yl­idene)thio­semicarbazone

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    The title compound, C10H12FN3S, crystallizes in the same space group (P21/c) as two polymorphic forms of 4-phenyl-1-(propan-2-yl­idene)thio­semicarbazone [Jian et al. (2005). Acta Cryst. E61, o653–o654; Venkatraman et al. (2005). Acta Cryst. E61, o3914–o3916]. The arrangement of mol­ecules relative to the twofold screw axes is similar to that in the crystal structure of the lower density polymorph. In the solid state, the mol­ecular conformation is stabilized by an intra­molecular N—H⋯N hydrogen bond. The mol­ecules form centrosymmetric R 2 2(8) dimers in the crystal through pairs of N—H⋯S hydrogen bonds

    The Echinococcus canadensis (G7) genome: A key knowledge of parasitic platyhelminth human diseases

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    Background: The parasite Echinococcus canadensis (G7) (phylum Platyhelminthes, class Cestoda) is one of the causative agents of echinococcosis. Echinococcosis is a worldwide chronic zoonosis affecting humans as well as domestic and wild mammals, which has been reported as a prioritized neglected disease by the World Health Organisation. No genomic data, comparative genomic analyses or efficient therapeutic and diagnostic tools are available for this severe disease. The information presented in this study will help to understand the peculiar biological characters and to design species-specific control tools. Results: We sequenced, assembled and annotated the 115-Mb genome of E. canadensis (G7). Comparative genomic analyses using whole genome data of three Echinococcus species not only confirmed the status of E. canadensis (G7) as a separate species but also demonstrated a high nucleotide sequences divergence in relation to E. granulosus (G1). The E. canadensis (G7) genome contains 11,449 genes with a core set of 881 orthologs shared among five cestode species. Comparative genomics revealed that there are more single nucleotide polymorphisms (SNPs) between E. canadensis (G7) and E. granulosus (G1) than between E. canadensis (G7) and E. multilocularis. This result was unexpected since E. canadensis (G7) and E. granulosus (G1) were considered to belong to the species complex E. granulosus sensu lato. We described SNPs in known drug targets and metabolism genes in the E. canadensis (G7) genome. Regarding gene regulation, we analysed three particular features: CpG island distribution along the three Echinococcus genomes, DNA methylation system and small RNA pathway. The results suggest the occurrence of yet unknown gene regulation mechanisms in Echinococcus. Conclusions: This is the first work that addresses Echinococcus comparative genomics. The resources presented here will promote the study of mechanisms of parasite development as well as new tools for drug discovery. The availability of a high-quality genome assembly is critical for fully exploring the biology of a pathogenic organism. The E. canadensis (G7) genome presented in this study provides a unique opportunity to address the genetic diversity among the genus Echinococcus and its particular developmental features. At present, there is no unequivocal taxonomic classification of Echinococcus species; however, the genome-wide SNPs analysis performed here revealed the phylogenetic distance among these three Echinococcus species. Additional cestode genomes need to be sequenced to be able to resolve their phylogeny.Fil: Maldonado, Lucas Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Assis, Juliana. Fundación Oswaldo Cruz; BrasilFil: Gomes Araújo, Flávio M.. Fundación Oswaldo Cruz; BrasilFil: Salim, Anna C. M.. Fundación Oswaldo Cruz; BrasilFil: Macchiaroli, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Cucher, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Camicia, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Fox, Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Rosenzvit, Mara Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Oliveira, Guilherme. Instituto Tecnológico Vale; Brasil. Fundación Oswaldo Cruz; BrasilFil: Kamenetzky, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Coumarin Derivatives: The Influence of Cycloalkyl Groups at the C-3 Position on Intermolecular Interactions—Synthesis, Structure and Spectroscopy

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    In this study, we explore the synthesis and solid-state characterization of four coumarin-3-carboxylic acid esters, each modified at the C-3 position with different cycloalkyl groups: cyclohexyl, menthyl, and iso-pulegyl. We conducted a detailed analysis of these compounds utilizing a variety of techniques such as a single-crystal X-ray diffraction, nuclear magnetic resonance (NMR), and Fourier-transform infrared (FTIR) spectroscopy. Additionally, we calculated the dipole moments for these molecules. Our findings include a thorough structural assessment, highlighting the role of noncovalent interactions through Full Interaction Maps and Hirshfeld surface analysis. This study reveals the critical influence of the weak C-H…O hydrogen bonds in determining the solid-state architecture of these esters, whereas π-π stacking interactions appear to be negligible among the studied derivatives

    1H-Tetrazol-5-amine and 1,3-thiazolidin-4-one derivatives containing 3-(trifluoromethyl)phenyl scaffold: Synthesis, cytotoxic and anti-HIV studies

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    On the basis of recently reported biologically active 3-(trifluoromethyl)phenylthioureas, a series of diaryl derivatives incorporating 1H-tetrazol-5-yl (1aâ\u80\u9311a, 1aâ\u80\u99â\u80\u9311aâ\u80\u99) and 1,3-thiazolidin-4-one (1bâ\u80\u9311b) scaffolds were synthesized. The synthesis pathway was confirmed by an X-ray crystallographic studies of 3aâ\u80\u99, 6a, 8a, 6b and 8b. The cytotoxicity against MT-4 cells and anti-HIV properties of new derivatives were evaluated. As compared to initial thiourea connections, the cyclisation reduced the cytotoxicity of compounds by 2â\u80\u9315 times. The most promising N-(4-nitrophenyl)-1H-tetrazol-5-amine 7a was found to be more active than the origin thiourea. Its cytotoxicity was evaluated on A549, HTB-140 and HaCaT cell lines using MTT assay. The compound shows significant influence on cancer, but not on normal cells. Obtained results can provide some constructive data for further designing of novel family of potentially bioactive analogs

    -aqua-dipropanol-copper(II)disodium}

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    Copyright © 2014 Anna E. Koziol et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. As a result of the direct synthesis through oxidative dissolution of metallic copper powder in the presence of phthalimide and sodium hydride a new polymeric bimetallic coordination compound [Cu(phthal)4Na2(PrOH)2H2O]n was synthesized and characterized by a single crystal X-ray crystallography and IR spectroscopy. The copper(II) ions have a distorted tetrahedral environment (CuN4), while the coordination polyhedra of two symmetrically independent sodium ions are distorted tetragonal pyramid (NaO5) and octahedron (NaO6). The alternating Cu and Na coordination spheres are bridged by the O atoms of the multidentate phthalimide anions. In the crystal lattice, columns of the polymeric complex are packed in the pseudo-hexagonal mode. The complex crystallizes in the triclinic space group P-1 with the unit cell parameters: a = 11.293(4) Å, b = 12.253(5) Å
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