Search results for "56"
showing 10 items of 1818 documents
Synthesis and antiproliferative activity of 3-(2-chloroethyl)-5-methyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4-(…
2015
Based on the encouraging results found for 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4-(3H)-one 7 previously tested by us, as well as the consideration that heterocycle fused tetrazepinones bearing the 2-chloroethyl substituent show a better cytotoxic profile than temozolomide and mitozolomide against human cancer cell lines which express the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT), in this paper we report the multistep synthesis and the biological study of 3-(2-cloroethyl)-5-methyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4-(3H)-one 10. Like compound 7, it was active on P-glycoprotein e…
Microbial deposits in the aftermath of the end-Permian mass extinction: A diverging case from the Mineral Mountains (Utah, USA)
2015
40 pages; International audience; The Lower Triassic Mineral Mountains area (Utah, USA) preserves diversified Smithian and Spathian reefs and bioaccumulations that contain fenestral-microbialites and various benthic and pelagic organisms. Ecological and environmental changes during the Early Triassic are commonly assumed to be associated with numerous perturbations (productivity changes, acidifica-tion, redox changes, hypercapnia, eustatism and temperature changes) post-dating the Permian–Triassic mass extinction. New data acquired in the Mineral Mountains sediments provide evidence to decipher the relationships between depositional environments and the growth and distribution of microbial …
First phenotypic description of Fasciola hepatica/Fasciola gigantica intermediate forms from the human endemic area of the Nile Delta, Egypt.
2007
Fasciola gigantica is the main fasciolid species in Africa; however, F. hepatica and F. gigantica overlap in some countries. Egypt deserves mentioning because of the emerging situation of human fascioliasis in the Nile Delta area. The morphometric characteristics of fasciolid adults infecting the main livestock species present in the Nile Delta human endemic area are analyzed through a computer image analysis system (CIAS) on the basis of standardized measurements known to be useful for the differentiation of both fasciolid species. This is the first time that such a study is performed in an African country and, therefore, the results are compared to (i) F. hepatica (European Mediterranean …
Tax burden borne by electricity and mining companies in Peru during 2010-2015 period
2018
O objetivo principal da pesquisa é quantificar a pressão fiscal suportada pelas empresas elétricas e de mineração que operam no Peru, no período 2010-2015, de tal forma que a existência de diferenças entre os dois setores econômicos analisados possa ser avaliada. Para este propósito, é apresentada uma descrição do setor elétrico e de mineração, bem como a evolução e influência que exercem sobre o crescimento econômico do Peru. Como elemento importante da investigação, foi realizada uma análise do arcabouço jurídico tributário que regula as atividades das empresas dos dois setores analisados, em especial, no tocante ao Imposto de Renda. O referencial teórico incorpora as principais referênci…
El aborto provocado: especial referencia en el Ordenamiento Canónico
2012
1. Regulación estatal. 1.1. Precedentes. 1.2. Legislación actual. 1.2.1 Aborto libre. 1.2.2. Sistema de indicaciones y plazos. 1.2.3. Aborto de menores de edad. 1.2.4. Objeción de conciencia. 1.2.5. Terminología ambigua. 1.2.6. Propuestas de futuro. 2. Regulación canónica. 2.1. El aborto es un pecado. 2.2. El aborto es un delito. 2.2.1. El aborto en el Código de 1917. 2.2.2. Legislación vigente. 2.2.2.1. Concepto. 2.2.2.2. Nuevos interrogantes. 2.2.2.3. Pena. 3. Consideraciones finales. 1. Regulation of the State. 1.1. Precedents. 1.2. Current legislation. 1.2.1. Free abortion. 1.2.2. System of instructions and deadlines. 1.2.3. Abortion of minors. 1.2.4. Conscientious objection. 1.2.5. Amb…
Synthesis, cytotoxicity, and inhibitory effects on tubulin polymerization of a new 3-heterocyclo substituted 2-styrylquinazolinones
2004
In order to study the influence of 3-substitution on the cytotoxic activity of 2-styrylquinazolinones, new 6-chloro-2-styryl-3-(heteroaryl)-4(3H)-quinazolinones were synthesized by refluxing equimolar amounts of 6-chloro-2-methyl-3-(heteroaryl)-4(3H)-quinazolinones and benzaldehyde in glacial acetic acid. At 1 microg ml(-1) concentration, almost all 2-styrylquinazolinones showed some cytotoxic activity against the L1210 and K562 leukemia cell lines. However, only 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone inhibited the growth of these cells by over 50%. This last compound was also the only member of the series that inhibited tubulin polymerization, with an IC(50) value of 5.8 v…
Unexpected multivalent display of proteins by temperature triggered self-assembly of elastin-like polypeptide block copolymers
2012
We report herein the unexpected temperature triggered self-assembly of proteins fused to thermally responsive elastin-like polypeptides (ELPs) into spherical micelles. A set of six ELP block copolymers (ELP(BC)) differing in hydrophilic and hydrophobic block lengths were genetically fused to two single domain proteins, thioredoxin (Trx) and a fibronectin type III domain (Fn3) that binds the α(v)β(3) integrin. The self-assembly of these protein-ELP(BC) fusions as a function of temperature was investigated by UV spectroscopy, light scattering, and cryo-TEM. Self-assembly of the ELP(BC) was unexpectedly retained upon fusion to the two proteins, resulting in the formation of spherical micelles …
3-Aryl-2-[1H-benzotriazol-1-yl]acrylonitriles: a novel class of potent tubulin inhibitors.
2011
During a screening for compounds that could act against Mycobacterium tuberculosis, a series of new cellular antiproliferative agents was identified. The most cytotoxic molecules were evaluated against a panel of human cell lines derived from hematological and solid human tumors. In particular, (E)-2-(1H-benzo[d] [1,2,3]triazol-1-yl)-3-(4-methoxyphenyl)acrylonitrile (1) was found to be of a potency comparable to etoposide and greater than 6-mercaptopurine in all cell lines tested. Accordingly, a synthesis of a new series of (E)-2-(5,6-dichloro-1H-benzo[d] [1,2,3]triazol-1-yl)-3-(4-R-phenyl)acrylonitriles was conducted in order to extend the studies of structure-activity relationship (SAR) f…
International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors
2015
The Adhesion family forms a large branch of the pharmacologically important superfamily of G protein-coupled receptors (GPCRs). As Adhesion GPCRs increasingly receive attention from a wide spectrum of biomedical fields, the Adhesion GPCR Consortium, together with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification, proposes a unified nomenclature for Adhesion GPCRs. The new names have ADGR as common dominator followed by a letter and a number to denote each subfamily and subtype, respectively. The new names, with old and alternative names within parentheses, are: ADGRA1 (GPR123), ADGRA2 (GPR124), ADGRA3 (GPR125), ADGRB1 (BAI1…
Synthesis and antiproliferative activity of new derivatives containing the polycyclic system 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3’,4’:2,3]azep…
2013
The reaction under reflux between 1-phenyl-3-R-5-methylaminopyrazoles and 2,5-hexanedione lead to 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3′,4′:2,3]azepino[4,5-f]azocine derivatives 3b–g. These unusual molecules show the structural complexity of many biologically active natural products and are endowed with the chemical diversity that is required in drug discovery. The compounds 3b,e were reduced by hydrogen in the presence of Palladium on activated charcoal to give the dihydro derivatives 5b,e. Compounds 3b–f and 5b,e were selected by the NCI to evaluate their in vitro antiproliferative activity against 60 human cell lines derived from nine clinically isolated cancer types (leukaemia, lu…