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排序方式: 共有252条查询结果,搜索用时 15 毫秒
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Valentina Gambino Giulia De Michele Oriella Venezia Pierluigi Migliaccio Valentina Dall'Olio Loris Bernard Simone Paolo Minardi Maria Agnese Della Fazia Daniela Bartoli Giuseppe Servillo Myriam Alcalay Lucilla Luzi Marco Giorgio Heidi Scrable Pier Giuseppe Pelicci Enrica Migliaccio 《Aging cell》2013,12(3):435-445
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Carolina Urquiola Marisol Vieites María H. Torre Mauricio Cabrera María Laura Lavaggi Hugo Cerecetto Mercedes González Adela López de Cerain Antonio Monge Pablo Smircich Beatriz Garat Dinorah Gambino 《Bioorganic & medicinal chemistry》2009,17(4):1623-1629
Four new palladium(II) complexes with the formula Pd(L)2, where L are quinoxaline-2-carbonitrile N1,N4-dioxide derivatives, were synthesized as a contribution to the chemistry and pharmacology of metal compounds with this class of pharmacologically interesting bioreductive prodrugs. Compounds were characterized by elemental, conductometric and thermogravimetric analyses, fast atom bombardment mass spectrometry (FAB-MS) and electronic, Fourier transform infrared (FTIR) and 1H-nuclear magnetic resonance spectroscopies. The complexes were subjected to cytotoxic evaluation on V79 cells in hypoxic and aerobic conditions. In addition, a preliminary study on interaction with plasmid DNA in normoxia was performed. Complexes showed different in vitro biological behavior depending on the nature of the substituent on the quinoxaline ring. Pd(L1)2 and Pd(L2)2, where L1 is 3-aminoquinoxaline-2-carbonitrile N1,N4-dioxide and L2 is 3-amino-6(7)-methylquinoxaline-2-carbonitrile N1,N4-dioxide, showed non selective cytotoxicity, being cytotoxic either in hypoxic or in aerobic conditions. On the other hand, Pd(L3)2, where L3 is 3-amino-6(7)-chloroquinoxaline-2-carbonitrile N1,N4-dioxide, resulted in vitro more potent cytotoxin in hypoxia (P = 5.0 μM) than the corresponding free ligand (P = 9.0 μM) and tirapazamine (P = 30.0 μM), the first bioreductive cytotoxic drug introduced into clinical trials. In addition, it showed a very good selective cytotoxicity in hypoxic conditions, being non-cytotoxic in normoxia. Its hypoxic cytotoxicity relationship value, HCR, was of the same order than those of other hypoxia selective cytotoxins (i.e., Mitomycine C, Misonidazole and the N-oxide RB90740). Interaction of the complexes with plasmid DNA in normoxia showed dose dependent ability to relax the negative supercoiled forms via different mechanisms. Pd(L2)2 introduced a scission event in supercoiled DNA yielding the circular relaxed form. Meanwhile, both Pd(L1)2 and Pd(L3)2 produced the loss of negative supercoils rendering a family of topoisomers with reduced electrophoretic mobility. Pd(L3)2 showed a more marked effect than Pd(L1)2. Indeed, for the highest doses assayed, Pd(L3)2 was even able to introduce positive supercoils on the plasmid DNA. 相似文献
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Giuseppe Gambino Sara De Pinto Lorenzo Tei Claudio Cassino Francesca Arena Eliana Gianolio Mauro Botta 《Journal of biological inorganic chemistry》2014,19(2):133-143
A dimeric GdAAZTA-like complex (AAZTA is 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid) bearing an adamantyl group (Gd2 L1) able to form strong supramolecular adducts with specific hosts such as β-cyclodextrin (β-CD), poly-β-CD, and human serum albumin (HSA) is reported. The relaxometric properties of Gd2 L1 were investigated in aqueous solution by measuring the 1H relaxivity as a function of pH, temperature, and magnetic field strength. The relaxivity of Gd2 L1 (per Gd atom) at 40 MHz and 298 K is 17.6 mM?1 s?1, a value that remains almost constant at higher fields owing to the great compactness and rigidity of the bimetallic chelate, resulting in an ideal value for the rotational correlation time for high-field MRI applications (1.5–3.0 T). The noncovalent interaction of Gd2 L1 with β-CD, poly-β-CD, and HSA and the relaxometric properties of the resulting host–guest adducts were investigated using 1H relaxometric methods. Relaxivity enhancements of 29 and 108 % were found for Gd2 L1–β-CD and Gd2 L1–poly-β-CD, respectively. Binding of Gd2 L1 to HSA (K A = 1.2 × 104 M?1) results in a remarkable relaxivity of 41.4 mM?1 s?1 for the bound form (+248 %). The relaxivity is only limited by the local rotation of the complex within the binding site, which decreases on passing from Gd2 L1–β-CD to Gd2 L1–HSA. Finally, the applicability of Gd2 L1 as tumor-targeting agent through passive accumulation of the HSA-bound adduct was evaluated via acquisition of magnetic resonance images at 1 T of B16-tumor-bearing mice. These experiments indicate a considerable signal enhancement (+160 %) in tumor after 60 min from the injection and a very low hepatic accumulation. 相似文献
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D Taruscio C Morciano P Laricchiuta P Mincarone F Palazzo CG Leo S Sabina R Guarino J Auld T Sejersen D Gavhed K Ritchie M Hilton-Boon J Manson PG Kanavos D Tordrup V Tzouma Y Le Cam J Senecat G Filippini S Minozzi C Del Giovane H Schünemann JJ Meerpohl B Prediger L Schell R Stefanov G Iskrov T Miteva-Katrandzhieva P Serrano-Aguilar L Perestelo-Perez MM Trujillo-Martín J Pérez-Ramos A Rivero-Santana A Brand H van Kranen K Bushby A Atalaia J Ramet L Siderius M Posada I Abaitua-Borda V Alonso Ferreira M Hens-Pérez FJ Manzanares 《Orphanet journal of rare diseases》2014,9(Z1):O14
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Cynthia Sarniguet Jeannette Toloza Micaella Cipriani Michel Lapier Marisol Vieites Yanis Toledano-Magaña Juan Carlos García-Ramos Lena Ruiz-Azuara Virtudes Moreno Juan Diego Maya Claudio Olea Azar Dinorah Gambino Lucía Otero 《Biological trace element research》2014,159(1-3):379-392
Parasitic illnesses are major causes of human disease and misery worldwide. Among them, both amebiasis and Chagas disease, caused by the protozoan parasites, Entamoeba histolytica and Trypanosoma cruzi, are responsible for thousands of annual deaths. The lack of safe and effective chemotherapy and/or the appearance of current drug resistance make the development of novel pharmacological tools for their treatment relevant. In this sense, within the framework of the medicinal inorganic chemistry, metal-based drugs appear to be a good alternative to find a pharmacological answer to parasitic diseases. In this work, novel ruthenium complexes [RuCl2(HL)(HPTA)2]Cl2 with HL = bioactive 5-nitrofuryl containing thiosemicarbazones and PTA?=?1,3,5-triaza-7-phosphaadamantane have been synthesized and fully characterized. PTA was included as co-ligand in order to modulate complexes aqueous solubility. In fact, obtained complexes were water soluble. Their activity against T. cruzi and E. histolytica was evaluated in vitro. [RuCl2(HL4)(HPTA)2]Cl2 complex, with HL4?=?N-phenyl-5-nitrofuryl-thiosemicarbazone, was the most active compound against both parasites. In particular, it showed an excellent activity against E. histolytica (half maximal inhibitory concentration (IC50)?=?5.2 μM), even higher than that of the reference drug metronidazole. In addition, this complex turns out to be selective for E. histolytica (selectivity index (SI) >38). The potential mechanism of antiparasitic action of the obtained ruthenium complexes could involve oxidative stress for both parasites. Additionally, complexes could interact with DNA as second potential target by an intercalative-like mode. Obtained results could be considered a contribution in the search for metal compounds that could be active against multiple parasites. 相似文献
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Cervello M Sanfilippo R Isola G Virruso L Scalia G Cammarata G Gambino R 《Development, growth & differentiation》1999,41(6):769-775
Sea urchin embryo micromeres when isolated and cultured in vitro differentiate to produce spicules. Although several authors have used this model, almost nothing is known about the signaling pathways responsible for initiating skeletogenesis. In order to investigate the potential involvement of phosphorylation events in spiculogenesis, the effect of inhibitors of protein kinases and phosphatases on skeleton formation was studied. Results obtained using both cultured micromeres and embryos revealed that protein tyrosine kinase and phosphatase inhibitors blocked skeleton formation, but not serine/threonine phosphatase inhibitors. The inhibitors showed a dose-dependent effect and when removed from micromere or embryo culture, spicule formation resumed. Inhibition of tyrosine phosphatases resulted in an increase in the tyrosine phosphorylation level of two major proteins and a modest decrease in the expression of the mRNA coding for type I fibrillar collagen. These findings strongly suggest that tyrosine phosphorylation and dephosphorylation is required for micromere differentiation and for normal skeletogenesis during sea urchin embryo development. 相似文献