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121.
Hidaka K Kimura T Ruben AJ Uemura T Kamiya M Kiso A Okamoto T Tsuchiya Y Hayashi Y Freire E Kiso Y 《Bioorganic & medicinal chemistry》2008,16(23):10049-10060
Plasmepsin (Plm) is a potential target for new antimalarial drugs, but most reported Plm inhibitors have relatively low antimalarial activities. We synthesized a series of dipeptide-type HIV protease inhibitors, which contain an allophenylnorstatine-dimethylthioproline scaffold to exhibit potent inhibitory activities against Plm II. Their activities against Plasmodium falciparum in the infected erythrocyte assay were largely different from those against the target enzyme. To improve the antimalarial activity of peptidomimetic Plm inhibitors, we attached substituents on a structure of the highly potent Plm inhibitor KNI-10006. Among the derivatives, we identified alkylamino compounds such as 44 (KNI-10283) and 47 (KNI-10538) with more than 15-fold enhanced antimalarial activity, to the sub-micromolar level, maintaining their potent Plm II inhibitory activity and low cytotoxicity. These results suggest that auxiliary substituents on a specific basic group contribute to deliver the inhibitors to the target Plm. 相似文献
122.
Silva AR Pinheiro AM Souza CS Freitas SR Vasconcellos V Freire SM Velozo ES Tardy M El-Bachá RS Costa MF Costa SL 《Cell biology and toxicology》2008,24(1):75-86
Astrocyte and microglia cells play an important role in the central nervous system (CNS). They react to various external aggressions
by becoming reactive and releasing neurotrophic and/or neurotoxic factors. Rutin is a flavonoid found in many plants and has
been shown to have some biological activities, but its direct effects on cells of the CNS have not been well studied. To investigate
its potential effects on CNS glial cells, we used both astrocyte primary cultures and astrocyte/microglia mixed primary cell
cultures derived from newborn rat cortical brain. The cultures were treated for 24 h with rutin (50 or 100 μmol/L) or vehicle
(0.5% dimethyl sulfoxide). Mitochondrial function on glial cells was not evidenced by the MTT test. However, an increased
lactate dehydrogenase activity was detected in the culture medium of both culture systems when treated with 100 μmol/L rutin,
suggesting loss of cell membrane integrity. Astrocytes exposed to 50 μmol/L rutin became reactive as revealed by glial fibrillary
acidic protein (GFAP) overexpression and showed a star-like phenotype revealed by Rosenfeld’s staining. The number of activated
microglia expressing OX-42 increased in the presence of rutin. A significant increase of nitric oxide (NO) was observed only
in mixed cultures exposed to 100 μmol/L rutin. Enhanced TNFα release was observed in astrocyte primary cultures treated with
100 μmol/L rutin and in mixed primary cultures treated with 50 and 100 μmol/L, suggesting different sensitivity of both activated
cell types. These results demonstrated that rutin affects astrocytes and microglial cells in culture and has the capacity
to induce NO and TNFα production in these cells. Hence, the impact of these effects on neurons in vitro and in vivo needs to be studied. 相似文献
123.
124.
By K. Meirelles Felizola Freire G. Rodrigues Alves Rocha I. Lemos Souza 《Zeitschrift fur angewandte Ichthyologie》2009,25(3):356-357
Length–weight relationships (TW = a TL b ) were estimated for fish species caught by bottom shrimp trawl in southern Bahia (Brazil) from March 2003 to February 2005. The results indicate that all 21 estimated relationships had a ' b ' within the usual range (2.5–3.5). Two new maximum size records were established: 19.2 cm for Odontognathus mucronatus and 16.1 cm for Stellifer brasiliensis . 相似文献
125.
Mateus G. Godoy Melissa L.E. Gutarra Fábio M. Maciel Shayany P. Felix Juliana V. Bevilaqua Olga L.T. Machado Denise M.G. Freire 《Enzyme and microbial technology》2009,44(5):317-322
The castor bean (Ricinus communis) represents a potential candidate for biodiesel production. The Petrobras Research Center is developing a biodiesel production process from castor bean seeds, in which an unwanted byproduct named castor bean waste is produced. This extremely alkaline waste is toxic and allergenic and, as such, poses a significant environmental problem. Solid-state fermentation (SSF) of castor bean waste was carried out to achieve ricin detoxification, reduce allergenic potential and stimulate lipase production. The fungus, Penicillium simplicissimum, an excellent lipase producer, was able to grow and produce lipase enzyme. After an optimization process, the maximum lipase activity achieved was 44.8 U/g. Moreover, the fungus P. simplicissimum was able to reduce the ricin content to non-detectable levels in addition to diminishing castor bean waste allergenic potential by approximately 16%. In this way, SSF of castor bean waste by P. simplicissimum may increase the utility of the waste by promoting enzyme production and eliminating the principal toxic element, ricin. 相似文献
126.
Tea obtained from leaves of Cymbopogon citratus (DC) Stapf is used for its anxiolytic, hypnotic and anticonvulsant properties in Brazilian folk medicine. Essential oil (EO) from fresh leaves was obtained by hydrodistillation and orally administered to Swiss male mice 30 min before experimental procedures. EO at 0.5 or 1.0 g/kg was evaluated for sedative/hypnotic activity through pentobarbital sleeping time, anxiolytic activity by elevated plus maze and light/dark box procedures and anticonvulsant activity through seizures induced by pentylenetetrazole and maximal electroshock. EO was effective in increasing the sleeping time, the percentage of entries and time spent in the open arms of the elevated plus maze as well as the time spent in the light compartment of light/dark box. In addition, EO delayed clonic seizures induced by pentylenetetrazole and blocked tonic extensions induced by maximal electroshock, indicating the elevation of the seizure threshold and/or blockage of seizures spread. These effects were observed in the absence of motor impairment evaluated on the rotarod and open field test. Our results are in accord with the ethnopharmacological use of Cymbopogon citratus, and after complementary toxicological studies it can support investigations assessing their use as anxiolytic, sedative or anticonvulsive agent. 相似文献
127.
Thomas Regnier Diganta Sarma Koushi Hidaka Usman Bacha Ernesto Freire Yoshio Hayashi Yoshiaki Kiso 《Bioorganic & medicinal chemistry letters》2009,19(10):2722-2727
A series of trifluoromethyl, benzothiazolyl or thiazolyl ketone-containing peptidic compounds as SARS-CoV 3CL protease inhibitors were developed and their potency was evaluated by in vitro protease inhibitory assays. Three candidates had encouraging results for the development of new anti-SARS compounds. 相似文献
128.
Carlos Gustavo Vasconcelos de Moraes Antonio Carlos Facio Jr. José Humberto Costa Roberto Freire Santiago Malta 《Journal of ocular biology, diseases, and informatics》2009,2(1):40-46
The purpose of this study was to describe the surgical outcomes and safety of intracameral bevacizumab during trabeculectomy in eyes with neovascular glaucoma. Pilot study included four eyes (four patients) with refractory neovascular glaucoma submitted to fornix-based trabeculectomy with adjunctive use of bevacizumab in the anterior chamber during the procedure. Patients were previously treated with panretinal photocoagulation as standard therapy. Variables evaluated were intraocular pressure, bleb appearance, iris neovascularization, intraoperative/postoperative complications, and visual outcomes. No intraoperative complication was observed. The mean follow-up period was 12.75 (range, 12–15 months). All eyes showed significant intraocular pressure control postoperatively. Iris neovascularization reduced significantly within 1 month after surgery. Mild anterior chamber inflammation was observed during follow-up in all eyes. No significant postoperative complication was observed, and no patient presented visual acuity deterioration. Intracameral bevacizumab may be used as an adjunctive therapy during trabeculectomy in eyes with neovascular glaucoma. 相似文献
129.
β-tubulins are structural components of microtubules and the targets of benzimidazole fungicides used to control many diseases of agricultural importance. Intron polymorphisms in the intron-rich genes of these proteins have been used in phylogeographic investigations of phytopathogenic fungi. In this work, we sequenced 2764 nucleotides of the β-tubulin gene (Pp tubB) in samples of Phakopsora pachyrhizi collected from seven soybean fields in Brazil. Pp tubB contained an open reading frame of 1341 nucleotides, including nine exons and eight introns. Exon length varied from 14 to 880 nucleotides, whereas intron length varied from 76 to 102 nucleotides. The presence of only four polymorphic sites limited the usefulness of Pp tubB for phylogeographic studies in P. pachyrhizi. The gene structures of Pp tubB and orthologous β-tubulin genes of Melampsora lini and Uromyces viciae-fabae were highly conserved. The amino acid substitutions in β-tubulin proteins associated with the onset of benzimidazole resistance in model organisms, especially at His (6) , Glu (198) and Phe (200) , were absent from the predicted sequence of the P. pachyrhizi β-tubulin protein. 相似文献
130.
Díaz-Jullien C Moreira D Sarandeses CS Covelo G Barbeito P Freire M 《Biochimica et biophysica acta》2011,1814(2):355-365
Prothymosin α (ProTα) is a multifunctional protein that, in mammalian cells, is involved in nuclear metabolism through its interaction with histones and that also has a cytosolic role as an apoptotic inhibitor. ProTα is phosphorylated by a protein kinase (ProTαK), the activity of which is dependent on phosphorylation. ProTα phosphorylation also correlates with cell proliferation. Mass spectrometric analysis of ProTαK purified from human tumor lymphocytes (NC37 cells) enabled us to identify this enzyme as the M2-type isoenzyme of pyruvate kinase. A study on the relationship between ProTαK activity and pyruvate kinase isoforms in NC37 cells and in other cell types confirmed that the M2 isoform is the enzyme responsible for ProTαK activity in proliferating cells. Yet, about 10% of the cellular pool of the M2 isoform shows specific affinity for ProTα and is responsible for ProTαK activity. This pool of M2 protein possesses no observable pyruvate kinase activity and changes its responses to various effectors of pyruvate kinase activity; however, these responses to PK effectors are maintained by the main cellular fraction containing the M2 isoform. Acquisition of ProTαK activity by M2 seems to be due to the phosphorylation of serine and threonine residues, which, besides being essential for its catalytic activity, induces a trimeric association of ProTαK. This association can be shifted to a tetrameric form by fructose 1, 6-bisphosphate, which results in a decrease in ProTαK activity. 相似文献