276 research outputs found
Antiprotozoal activity of novel diaryliminophenazines
No full textRecently, we synthesized a set of novel iminofenazines bearing a bicyclic basic head linked through an alkyl chain to the imino nitrogen in position 3 on the phenazine nucleus (Fig.1).
Most of these compounds inhibited the growth of different species of Leishmania promastigotes as well as of chloroquine sensitive (CQ-S) and chloroquine resistant (CQ-R) strains of P. falciparum with IC50 in the submicromolar range. Unfortunately, these compounds exhibited also a significant toxicity against the human endothelial cell line HMEC-1 with IC50 in the low micromolar range and with a consequent low selectivity index.
Figure1.Structures of the previously synthesized compounds.
To continue the studies on the antiprotozoal potentialities of this class of compounds and with the aim to improve their activity and selectivity on protozoa, we have now synthesized novel compounds characterized by the replacement of the aniline moiety in pos. 2 of the phenazine nucleus with an aminopyridine, and/or by a quaternarization of the basic nitrogen in the side chain with a methyl group (Fig.2).
Figure 2. Structures of the new compounds synthesized.
The in vitro activity of the new compounds on Leishmania promastigotes and on CQ-S and CQ-R strains of P. falciparum, as well as on the HMEC-1 cell line will be presented and discussed.
References
[1] A. Barteselli, M. Gavazzi, N. Basilico, S. Parapini, D. Taramelli, A. Sparatore. Clofazimine analogs with antileishmanial and antimalarial activities. XXII National Meeting on Medicinal Chemistry, Roma 2013
Materiali degli scavi taramelliani dal santuario nuragico di Santa Vittoria di Serri dai depositi della Soprintendenza
No full textNell’ambito del progetto “Saperi condivisi. Prospettive di ricerca sulla Preistoria e Protostoria in Europa” dell’Istituto Italiano di Preistoria e Protostoria, è stato possibile analizzare un lotto di materiali archeologici, provenienti dagli scavi nel santuario di Santa Vittoria di Antonio Taramelli dei primi anni del ’900 e conservati nei depositi della Soprintendenza ABAP di Cagliari. Lo studio dei materiali, in parte inediti, ha permesso di ricostruire con maggiore precisione la vita nel villaggio santuariale e inquadrarli in un contesto cronologico più preciso; in questa sede sarà analizzato il contesto della Capanna A o degli altarini, ubicata tra il tempio a pozzo e il recinto delle feste.Within the project “Shared knowledge. Research Perspectives on Prehistory and Early History in Europe” of the Italian Institute of Prehistory and Protohistory, it was possible to analyze a lot of archaeological materials, coming from the excavations in the sanctuary of Santa Vittoria by Antonio Taramelli of the early 20th century and kept in the deposits of the Soprintendenza ABAP of Cagliari. The study of the materials, partly unpublished, has allowed us to reconstruct more precisely the life in the sanctuary village and place them in a more precise chronological context: here we analyse the context of the “Capanna A” or of the small altars, located between the well temple and the party enclosure
Motifs resembling hepatocyte nuclear factor 1 and activator protein 3 mediate the tissue specificity of the human plasminogen gene
No full textPlasminogen is one of the key elements in the fibrinolytic process. Like most of the gene products that participate in such reactions and which interact with plasminogen, the site of its synthesis is mainly confined to the hepatocyte. Plasminogen RNA has additionally been detected in kidney and very low amounts also in testes. Deletional analysis has indicated that two 5' sequences located within 2.5 kb of the first ATG are responsible for the transcriptional activation and the tissue specificity of the expression of the gene. By DNase protection and gel mobility shift assays with HepG2 nuclear extracts, the two sequences were localized and found to be the recognition sites for the widely known hepatocyte nuclear factor 1 (HNF-1) a trans-acting factor, and a nuclear factor like activator protein 3 (AP-3). The first one lies in a rather unusual position, i.e. within the 5'-untranslated region. The latter is located further upstream in a region between -2200 and -2100 from the plasminogen mRNA cap site. Moreover, site-directed mutagenesis coupled by functional experiments in HepG2 cells has demonstrated a synergism between these two positively acting elements in controlling the transcription of the human plasminogen gene
Identification of the 5' end ofthe gene encoding a human insulin-responsive glucose transporter
No full textAre Tumor Suppressor Genes Playing a Role in the Deregulation of Tissue Organization in Cancer?
No full textDefinition of the transcription initiation site of human plasminogengene in liver and non hepatic cell lines
No full textWe have mapped the cap site of the human plasminogen mRNA by primer extension and PCR techniques and found that it is located at position -161 relative to the first ATG, 97 bases upstream to the 5' end of the previously isolated cDNA clone. Seven human hepatic and non hepatic cell lines and fresh liver cells were tested for human plasminogen mRNA expression: the liver and the liver derived HepG2 cell line represent the major site of plasminogen RNA synthesis while the other cell lines (Hep3B, HeLa, IMR, 293 CaCo and SW626) show much lower levels
Reporter gene analysis of four DNaseI hypersensitive sites in the plasminogen/apolipoprotein(a) intergenic region.
No full textModified quaternary ammonium salts as potential antimalarial agents
No full textA series of new quaternary ammonium salts containing a polyconjugated moiety has been synthesized and characterized; their biological activity as potential antimalarial agents was investigated, as well. All compounds were screened against chloroquine resistant W-2 (CQ-R) and chloroquine sensitive, D-10 (CQ-S) strains of Plasmodium falciparum showing IC50 in the submicromolar range and low toxicity against human endothelial cells
The inhibition of lymphocyte stimulation by autologous human metastatic melanoma cells correlates with the expression of HLA-DR antigens on the tumor cells
No full textPrevious studies indicated that peripheral blood lymphocytes from patients (Pt-PBL) with lymph node metastatic melanomas proliferated in vitro and developed into tumor-restricted cytotoxic lymphocytes in response to alloantigens or interleukin 2 (IL-2). However, Pt-PBL were not stimulated by irradiated autologous metastatic melanoma (Auto-Me) cells. In the present study we report that the lack of stimulatory activity of Auto-Me cells may be due to a suppressive effect exerted by Auto-Me cells on the responder lymphocytes. In fact, we found that in 62% of cases examined, the addition of 5-10% Auto-Me cells to Pt-PBL cultures strongly inhibited both proliferation and the generation of tumor cytotoxic lymphocytes induced by alloantigens or IL-2. The inhibition was dose-dependent and tumor-restricted, and was not due either to toxicity, medium depletion or IL-2 absorption by Auto-Me cells. Normal fibroblasts, K562 cells and autologous E-lymphocytes were not suppressive. Auto-Me cells were able to inhibit Pt-PBL responses only when added during the first 24 h of culture and not later. Phenotypic analysis of Auto-Me cells using monoclonal antibodies directed against HLA-A,B,C, HLA-DR and melanoma-associated antigens revealed that the expression of high levels of DR antigens on Auto-Me cells was associated with an elevated suppressive activity. Conversely, Auto-Me cells with low or undetectable levels of DR antigens were not inhibitory. Furthermore, the increased expression of DR antigens on Auto-Me cells obtained by in vitro treatment with human interferon gamma (IFN-gamma) also resulted in an increased suppressive activity. We conclude that HLA-DR+ metastatic melanoma cells can interfere with the generation of an anti-tumor immune response, thus potentially favoring the escape of the tumor from the host's control mechanism
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