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排序方式: 共有160条查询结果,搜索用时 15 毫秒
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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
3.
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
4.
G. Mazzocchi Claudia Robba Anna S. Belloni P. Rigotti Anna M. Gambino Prof. G. G. Nussdorfer 《Cell and tissue research》1976,168(1):1-9
Summary The effects of chronic administration of ACTH (up to 36 consecutive days) on the mitochondria of the zona reticularis of the rat adrenal cortex were investigated by stereologic techniques. It was found that ACTH induces two phases of hypertrophy of mitochondria alternating with two proliferative stages, which are associated with a significant decrease in the average volume of the organelles. It is suggested that, as in the zona fasciculata, ACTH controls the processes of growth and division of mitochondria in the zona reticularis. The mechanism underlying this action of ACTH as well as the differences between the responses to ACTH of the mitochondrial population of the two adrenal zones are discussed in the light of evidence indicating that mitochondria contain a complete genetic apparatus largely independent of nuclear control.The authors wish to thank Miss A. Coi and Mr. G. Gottardo for their excellent technical assistance. This work was partly supported by a contract with the CNR (C.T. 73.00663.04) 相似文献
5.
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
6.
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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Annibale A. Puca Anna Ferrario Anna Maciag Giulia Accardi Anna Aiello Caterina Maria Gambino Giuseppina Candore Calogero Caruso Aryan M. Namboodiri Janardan P. Pandey 《Immunity & ageing : I & A》2018,15(1):26
Background
The aim of this study was to analyse the role of GM allotypes, i.e. the hereditary antigenic determinants expressed on immunoglobulin polypeptide chains, in the attainment of longevity. The role played by immunoglobulin allotypes in the control of immune responses is well known as well as the role of an efficient immune response in longevity achievement. So, it is conceivable that particular GM allotypes may contribute to the generation of an efficient immune response that supports successful ageing, hence longevity.Methods
In order to show if GM allotypes play a role in the achievement of longevity, we typed the DNA of 95 Long-living individuals (LLIs) and 96 young control individuals (YCs) from South Italy for GM3/17 and GM23+/? alleles.Results
To demonstrate the role of GM allotypes in the attainment of longevity we compared genotype and allele frequencies of GM allotypes between LLIs and YCs. A global chi-square test (3?×?2) shows that the distribution of genotypes at the GM 3/17 locus is highly significantly different in LLIs from that observed in YCs (p?<?0.0001). The 2?×?2 chi-square test shows that the carriers of the GM3 allele contribute to this highly significant difference. Accordingly, GM3 allele is significantly overrepresented in LLIs. No significant differences were instead observed regarding GM23 allele.Conclusion
These preliminary results show that GM3 allotype is significantly overrepresented in LLIs. To best of our knowledge, this is the first study performed to assess the role of GM allotypes in longevity. So, it should be necessary to verify the data in a larger sample of individuals to confirm GM role in the attainment of longevity.9.
Martínez H Rodríguez-Larralde A Izaguirre MH De Guerra DC 《Human biology; an international record of research》2007,79(2):201-213
The present Venezuelan population is the product of admixture of Amerindians, Europeans, and Africans, a process that was not homogeneous throughout the country. Blood groups, short tandem repeats (STRs), mtDNA, and Y-chromosome markers have been used successfully in admixture studies, but few such studies have been conducted in Venezuela. In this study we aim to estimate the admixture components of samples from two different socioeconomic levels from Caracas, Venezuela's capital city, compare their differences, and infer sexual asymmetry in the European Amerindian union patterns. Gene frequencies for blood groups ABO and Rh (CDE) and for the STRs VWA, F13A01, and FES/FPS and mtDNA and Y-chromosome haplogroups were studied in a sample of 60 individuals living in Caracas, taken from a private clinic (high socioeconomic level), and 50 individuals, also living in Caracas, drawn from a public maternity clinic (low socioeconomic level). The admixture analysis for the five autosomal markers gives a high European component (0.78) and an almost negligible African sub-Saharan component (0.06) for the high socioeconomic level, whereas for the low socioeconomic level the sub-Saharan, European, and Amerindian components were 0.21, 0.42, and 0.36, respectively. Estimates of admixture based on mtDNA and Y-chromosome markers reveal that the Amerindian contribution to these Caracas samples is almost entirely through females, because the Y-chromosome Amerindian and African sub-Saharan chromosomes found in this study were scarce. Our study reveals that the identification of the grandparents' geographic origin is an important methodological aspect to take into account in genetic studies related to the reconstruction of historical events. 相似文献
10.
Naturally occurring neuronal death (NOND) is an essential phenomenon during the course of normal development of the nervous system. Studies in vivo and on organotypic cultures have helped to elucidate the basic histological and ultrastructural features, as well as the main cellular mechanisms of NOND in several areas of the brain. This review examines the existing evidence about the two waves of apoptotic cell death that affect the different types of cerebellar neurons in normal development and certain pathological conditions. The first wave regards neuronal progenitors and pre-migratory neuroblasts, the second post-migratory neuroblasts and mature neurons. The underlying cellular and molecular mechanisms are discussed critically also in the light of their relevance to neurodegenerative diseases. 相似文献