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141.
Angelina M. de Almeida Thiago Nascimento Bianca S. Ferreira Pedro P. de Castro Vânia L. Silva Claúdio G. Diniz Mireille Le Hyaric 《Bioorganic & medicinal chemistry letters》2013,23(10):2883-2887
We report in this work the preparation and in vitro antimicrobial evaluation of novel amphiphilic aromatic amino alcohols synthesized by reductive amination of 4-alkyloxybenzaldehyde with 2-amino-2-hydroxymethyl-propane-1,3-diol. The antibacterial activity was determined against four standard strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa) and 21 clinical isolates of methicillin-resistant Staphylococcus aureus. The antifungal activity was evaluated against four yeast (Candida albicans, Candida tropicalis, Candida glabrata and Candida parapsilosis). The results obtained showed a strong positive correlation between the lipophilicity and the antibiotic activity of the tested compounds. The best activities were obtained against the Gram-positive bacteria (MIC = 2–16 μg ml?1) for the five compounds bearing longer alkyl chains (4c–g; 8–14 carbons), which were also the most active against Candida (MIC = 2–64 μg ml?1). Compound 4e exhibited the highest levels of inhibitory activity (MIC = 2–16 μg ml?1) against clinical isolates of MRSA. A concentration of twice the MIC resulted in bactericidal activity of 4d against 19 of the 21 clinical isolates. 相似文献
142.
Martin Mendez Thomas A. Jefferson Sergios‐Orestis Kolokotronis Michael Krützen Guido J. Parra Tim Collins Giana Minton Robert Baldwin Per Berggren Anna Särnblad Omar A. Amir Vic M. Peddemors Leszek Karczmarski Almeida Guissamulo Brian Smith Dipani Sutaria George Amato Howard C. Rosenbaum 《Molecular ecology》2013,22(23):5936-5948
The conservation of humpback dolphins, distributed in coastal waters of the Indo‐West Pacific and eastern Atlantic Oceans, has been hindered by a lack of understanding about the number of species in the genus (Sousa) and their population structure. To address this issue, we present a combined analysis of genetic and morphologic data collected from beach‐cast, remote‐biopsied and museum specimens from throughout the known Sousa range. We extracted genetic sequence data from 235 samples from extant populations and explored the mitochondrial control region and four nuclear introns through phylogenetic, population‐level and population aggregation frameworks. In addition, 180 cranial specimens from the same geographical regions allowed comparisons of 24 morphological characters through multivariate analyses. The genetic and morphological data showed significant and concordant patterns of geographical segregation, which are typical for the kind of demographic isolation displayed by species units, across the Sousa genus distribution range. Based on our combined genetic and morphological analyses, there is convincing evidence for at least four species within the genus (S. teuszii in the Atlantic off West Africa, S. plumbea in the central and western Indian Ocean, S. chinensis in the eastern Indian and West Pacific Oceans, and a new as‐yet‐unnamed species off northern Australia). 相似文献
143.
Daniela Volcan Almeida Camila de Martinez Gaspar Martins M��rcio de Azevedo Figueiredo Carlos Frederico Ceccon Lanes Adalto Bianchini Luis Fernando Marins 《Transgenic research》2013,22(1):75-88
Growth hormone (GH) transgenic fish are at a critical step for possible approval for commercialization. Since this hormone is related to salinity tolerance in fish, our main goal was to verify whether the osmoregulatory capacity of the stenohaline zebrafish (Danio rerio) would be modified by GH-transgenesis. For this, we transferred GH-transgenic zebrafish (T) from freshwater to 11 ppt salinity and analyzed survival as well as relative changes in gene expression. Results show an increased mortality in T versus non-transgenic (NT) fish, suggesting an impaired mechanism of osmotic acclimation in T. The salinity effect on expression of genes related to osmoregulation, the somatotropic axis and energy metabolism was evaluated in gills and liver of T and NT. Genes coding for Na+, K+-ATPase, H+-ATPase, plasma carbonic anhydrase and cytosolic carbonic anhydrase were up-regulated in gills of transgenics in freshwater. The growth hormone receptor gene was down-regulated in gills and liver of both NT and T exposed to 11 ppt salinity, while insulin-like growth factor-1 was down-regulated in liver of NT and in gills of T exposed to 11 ppt salinity. In transgenics, all osmoregulation-related genes and the citrate synthase gene were down-regulated in gills of fish exposed to 11 ppt salinity, while lactate dehydrogenase expression was up-regulated in liver. Na+, K+-ATPase activity was higher in gills of T exposed to 11 ppt salinity as well as the whole body content of Na+. Increased ATP content was observed in gills of both NT and T exposed to 11 ppt salinity, being statistically higher in T than NT. Taking altogether, these findings support the hypothesis that GH-transgenesis increases Na+ import capacity and energetic demand, promoting an unfavorable osmotic and energetic physiological status and making this transgenic fish intolerant of hyperosmotic environments. 相似文献
144.
Claudia Mara Maciel-Rezende Letícia de Almeida Éderson D’Martin Costa Francieli Ribeiro Pires Karina Ferreira Alves Cláudio Viegas Junior Danielle Ferreira Dias Antônio Carlos Doriguetto Marcos José Marques Marcelo Henrique dos Santos 《Bioorganic & medicinal chemistry》2013,21(11):3114-3119
Nine O-alkyl and O-prenyl derivatives were synthesized from commercial 2,4-dihydroxybenzophenone, 4,e4,4′-dihydroxybenzophenone and were evaluated for their leishmanicidal activity against promastigote forms of Leishmania amazonensis, as well their toxicity in murine macrophages. All derivatives exhibited better biological activity than their hydroxylated benzophenones precursors, and new compound LFQM-123 (3c) was 250-fold more active than its precursor 4,4′-dihydroxybenzophenone (3). Moreover, some of the results were comparable to the standard drug Amphotericin B, suggesting that the increase in lipophilicity could facilitate protozoa membrane permeation. In this study we confirmed that benzophenone derivatives exhibit leishmanicidal properties, with relatively low toxicity, and thus could be exploited as promise prototypes for the design and development of new drug for the treatment of leishmaniasis. 相似文献
145.
The severe acute respiratory syndrome coronavirus (SARS-CoV) envelope spike (S) glycoprotein is responsible for the fusion between the membranes of the virus and the target cell. In the case of the S2 domain of protein S, it has been found a highly hydrophobic and interfacial domain flanked by the heptad repeat 1 and 2 regions; significantly, different peptides pertaining to this domain have shown a significant leakage effect and an important plaque formation inhibition, which, similarly to HIV-1 gp41, support the role of this region in the fusion process. Therefore, we have carried out a study of the binding and interaction with model membranes of a peptide corresponding to segment 1073–1095 of the SARS-CoV S glycoprotein, peptide SARSL in the presence of different membrane model systems, as well as the structural changes taking place in both the lipid and the peptide induced by the binding of the peptide to the membrane. Our results show that SARSL strongly partitions into phospholipid membranes and organizes differently in lipid environments, displaying membrane activity modulated by the lipid composition of the membrane. These data would support its role in SARS-CoV mediated membrane fusion and suggest that the region where this peptide resides could be involved in the merging of the viral and target cell membranes. 相似文献
146.
Dr Raquel Marin Cristina M. Ramírez Cristina M. Ramírez Miriam González Elena González-Muñoz 《Molecular membrane biology》2013,30(2):148-160
Voltage-dependent anion channel (VDAC) is a porin known by its role in metabolite transport across mitochondria and participation in apoptotic processes. Although traditionally accepted to be located within mitochondrial outer membrane, some data has also reported its presence at the plasma membrane level where it seems to participate in regulation of normal redox homeostasis and apoptosis. Here, exposure of septal SN56 and hippocampal HT22 cells to specific anti-VDAC antibodies prior to amyloid beta (Aβ) peptide was observed to prevent neurotoxicity. In these cell lines, we identified a VDAC form associated with the plasma membrane that seems to be particularly abundant in caveolae. The two membrane-related isoforms of estrogen receptor α (mERα) (80 and 67 kDa), known in SN56 cells to participate in estrogen-induced neuroprotection against Aβ injury, were also observed to be present in caveolae. Interestingly, we demonstrated for the first time that both VDAC and mERα interact at the plasma membrane of these neurons as well as in microsomal fractions of the corresponding murine septal and hippocampal tissues. These proteins were also shown to associate with caveolin-1, thereby corroborating their presence in caveolar microdomains. Taken together, these results suggest that VDAC-mERα association at the plasma membrane level may participate in the modulation of Aβ-induced cell death. 相似文献
147.
Eliana Alves Maria A.F. Faustino João P.C. Tomé Maria G.P.M.S. Neves Augusto C. Tomé José A.S. Cavaleiro Ângela Cunha Newton C.M. Gomes Adelaide Almeida 《Bioorganic & medicinal chemistry》2013,21(14):4311-4318
Light activation of photosensitizing dyes in presence of molecular oxygen generates highly cytotoxic reactive oxygen species leading to cell inactivation. Nucleic acids are molecular targets of this photodynamic action but not considered the main cause of cell death. The in vivo effect of the photodynamic process on the intracellular nucleic acid content of Escherichia coli and Staphylococcus warneri was evaluated herein.Two cationic porphyrins (Tetra-Py+-Me and Tri-Py+-Me-PF) were used to photoinactivate E. coli (5.0 μM; 108 cells mL?1) and S. warneri (0.5 μM; 108 cells mL?1) upon white light irradiation at 4.0 mW cm?2 for 270 min and 40 min, respectively. Total nucleic acids were extracted from photosensitized bacteria after different times of irradiation and analyzed by agarose gel electrophoresis. The double-stranded DNA was quantified by fluorimetry and the porphyrin binding to bacteria was determined by spectrofluorimetry.E. coli was completely photoinactivated with both porphyrins (5.0 μM), whereas S. warneri was only completely inactivated by Tri-Py+-Me-PF (0.5 μM). The hierarchy of nucleic acid changes in E. coli was in the order: 23S rRNA > 16S rRNA > genomic DNA. The nucleic acids of S. warneri were extensively reduced after 5 min with Tri-Py+-Me-PF but almost unchanged with Tetra-Py+-Me after 40 min of irradiation. The amount of Tri-Py+-Me-PF bound to E. coli after washing the cells is higher than Tetra-Py+-Me and the opposite was observed for S. warneri. The binding capacity of the photosensitizers is not directly related to the PDI efficiency or nucleic acid reduction and this reduction occurs in parallel with the decrease of surviving cells. 相似文献
148.
Carlos M.G. Azevedo Carlos M.M. Afonso Diana Sousa Raquel T. Lima M. Helena Vasconcelos Madalena Pedro João Barbosa Arlene G. Corrêa Salette Reis Madalena M.M. Pinto 《Bioorganic & medicinal chemistry》2013,21(11):2941-2959
A promising antitumor xanthone derivative was optimized following a multidimensional approach that involved the synthesis of 17 analogues, the study of their lipophilicity and solubility, and the evaluation of their growth inhibitory activity on four human tumor cell lines. A new synthetic route for the hit xanthone derivative was also developed and applied for the synthesis of its analogues. Among the used cell lines, the HL-60 showed to be in general more sensitive to the compounds tested, with the most potent compound having a GI50 of 5.1 μM, lower than the hit compound. Lipophilicity was evaluated by the partition coefficient (Kp) of a solute between buffer and two membrane models, namely liposomes and micelles. The compounds showed a log Kp between 3 and 5 and the two membrane models showed a good correlation (r2 = 0.916) between each other. Studies concerning relationship between solubility and structure were developed for the hit compound and 5 of its analogues. 相似文献
149.