Differential expression on mitochondrial tryparedoxin peroxidase (mTcTXNPx) in Trypanosoma cruzi after ferrocenyl diamine hydrochlorides treatments

Resistance to benznidazole in certain strains of Trypanosoma cruzi may be caused by the increased production of enzymes that act on the oxidative metabolism, such as mitochondrial tryparedoxin peroxidase which catalyses the reduction of peroxides. This work presents cytotoxicity assays performed with ferrocenyl diamine hydrochlorides in six different strains of T. cruzi epimastigote forms (Y, Bolivia, SI1, SI8, QMII, and SIGR3). The last four strains have been recently isolated from triatominae and mammalian host (domestic cat). The expression of mitochondrial tryparedoxin peroxidase was analyzed by the Western blotting technique using polyclonal antibody anti mitochondrial tryparedoxin peroxidase obtained from a rabbit immunized with the mitochondrial tryparedoxin peroxidase recombinant protein. All the tested ferrocenyl diamine hydrochlorides were more cytotoxic than benznidazole. The expression of the 25.5 kDa polypeptide of mitochondrial tryparedoxin peroxidase did not increase in strains that were more resistant to the ferrocenyl compounds (SI8 and SIGR3). In addition, a 58 kDa polypeptide was also recognized in all strains. Ferrocenyl diamine hydrochlorides showed trypanocidal activity and the expression of 25.5 kDa mitochondrial tryparedoxin peroxidase is not necessarily increased in some T. cruzi strains. Most likely, other mechanisms, in addition to the over expression of this antioxidative enzyme, should be involved in the escape of parasites from cytotoxic oxidant agents. Keywords: Trypanosoma cruzi, Ferrocenyl diamine hydrochlorides, Mitochondrial tryparedoxin peroxidase (mTcTXNPx), Oxidative stress mechanism

Theoretical Studies of the Tautomerism in 3-(2-R-Phenylhydrazono)-naphthalene- 1,2,4-triones: Synthesis of Copper(II) Complexes and Studies of Antibacterial and Antitumor Activities

Submitted by Sandra Infurna ([email protected]) on 2018-11-29T13:02:09Z No. of bitstreams: 1 jussarap_barbosa_etal_IOC_2010.pdf: 1564535 bytes, checksum: b114a73b75a02eda0887520d01d69d53 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-11-29T13:12:59Z (GMT) No. of bitstreams: 1 jussarap_barbosa_etal_IOC_2010.pdf: 1564535 bytes, checksum: b114a73b75a02eda0887520d01d69d53 (MD5)Made available in DSpace on 2018-11-29T13:12:59Z (GMT). No. of bitstreams: 1 jussarap_barbosa_etal_IOC_2010.pdf: 1564535 bytes, checksum: b114a73b75a02eda0887520d01d69d53 (MD5) Previous issue date: 2010Universidade Federal Fluminense. Instituto de Química. Campus do Valonguinho, Niterói. RJ, Brasil.Universidade Federal Fluminense. Instituto de Química. Campus do Valonguinho, Niterói. RJ, Brasil.Universidade Federal Fluminense. Instituto de Química. Campus do Valonguinho, Niterói. RJ, Brasil.Universidade Federal Fluminense. Instituto de Química. Campus do Valonguinho, Niterói. RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Instituto de Química. Campus do Valonguinho, Niterói. RJ, Brasil.Universidade Federal Fluminense. Instituto de Química. Campus do Valonguinho, Niterói. RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.Universidade Federal do Ceará. Depto de Fisiologia e Farmacologia. Campus do Porangabussu, Fortaleza, CE, Brasil.Universidade Federal do Ceará. Depto de Fisiologia e Farmacologia. Campus do Porangabussu, Fortaleza, CE, Brasil.Universidade Federal do Ceará. Depto de Fisiologia e Farmacologia. Campus do Porangabussu, Fortaleza, CE, Brasil.Universidade Federal do Ceará. Depto de Fisiologia e Farmacologia. Campus do Porangabussu, Fortaleza, CE, Brasil.Universidade Federal do Paraná. Departamento de Química. Curitiba, PR, Brasil.DFT calculations using the B3LYP and PBE1PBE functionals with the standard 6-31G(d) and 6-311+G(2d,p) basis sets were carried out for the 3-(2-phenylhydrazone)-naphthalene-1,2,4-trione system in solution (dmso) and in the gas phase, and showed the keto-hydrazone forms (rotamers Ia and Ib) to be more stable than the enol-azo forms (rotamers IIa and IIb, by about 14 kcal mol-1) and III (by approximately 6 kcal mol-1), independently of the nature of the substituent in the phenylene ring. These results were confirmed by spectroscopic data on the derivatives HL1-HL13, obtained from 2-hydroxy-1,4-naphthoquinone and arylamines (R = 4-OMe, 4-N2-C6H5, 4-Cl, 4-I, 3-I, 2-I, 4-COOH, 3-COOH, 4-CN, 3-CN, 4-NO2, 3-NO2, 2-NO2). The in vitro antitumor (against SF-295, HCT-8, MDAMB-435 and HL-60 cancer cell lines) and antibacterial activities (Bacillus cereus, Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa) of compounds HL1-HL13 and of their respective copper(II) complexes, [Cu(L1-13)2], were tested. In general, these compounds exhibited low antibacterial activity, except for HL5 (R = 3-I), more active than the control; however, the corresponding complex was inactive. In contrast, increased cytotoxicity was observed upon complexation. Complex [Cu(L13)2] (R = 3-NO2) presented moderate cytotoxicity against human leukemia (HL-60).Cálculos teóricos utilizando os funcionais B3LYP e PBE1PBE e as bases 6-31G(d) e 6-311+G(2d,p) para o sistema 3-(2-fenil-hidrazona)-naftaleno-1,2,4-triona, em solução (dmso) e em fase gasosa, evidenciaram, em ambos os casos, a maior estabilidade da forma ceto-hidrazona (rotâmeros Ia e Ib) comparada às formas enol-azo (rotâmeros IIa/IIb, por volta de 14 kcal mol-1) e III (aproximadamente 6 kcal mol-1). A natureza do substituinte no grupo fenil não influenciou a estabilidade relativa dos tautômeros. Estes resultados foram confirmados por dados espectroscópicos dos derivados HL1-HL13, sintetizados a partir da 2-hidroxi-1,4-naftoquinona e arilaminas (R = 4-OMe, 4-N2-C6H5, 4-Cl, 4-I, 3-I, 2-I, 4-COOH, 3-COOH, 4-CN, 3-CN, 4-NO2, 3-NO2, 2-NO2). A avaliação da atividade anticâncer in vitro (contra linhagens de células cancerosas SF-295, HCT‑8, MDAMB-435 e HL-60) e bactericida (Bacillus cereus, Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia e Pseudomonas aeruginosa) dos compostos HL1-HL13 e dos seus respectivos complexos de cobre(II), [Cu(L1-13)2], foi avaliada. Em geral a atividade bactericida foi baixa, exceto para o derivado HL5 (R = 3-I), mais ativo do que o controle; entretanto, seu complexo não foi ativo. Por outro lado, a complexação levou, em geral, ao aumento da atividade antitumoral dos pré-ligantes. O complexo [Cu(L13)2] (R = 3-NO2) apresentou moderada citotoxicidade contra leucemia humana (HL-60)

Avaliação da debulha mecânica em sementes de milho Evaluation of mechanical thrashing processing in corn seeds

No estado da Paraíba, as perdas de sementes e grãos de milho (Zea mays L.) provocadas principalmente pela colheita, debulha mecânica, beneficiamento e processos subseqüentes, são da ordem de 20%, acarretando prejuízos econômicos ao estado. Assim, estudaram-se as danificações decorrentes da debulha mecânica e da passagem das sementes de milho, variedades Cruzeta e Sertanejo, pelas diferentes etapas do beneficiamento. Para avaliar os danos provocados às sementes, utilizou-se uma debulhadora estacionária trabalhando a rotações de 520, 600 e 700 rpm, obtidas pela variação da aceleração do motor do trator ao qual a debulhadora se achava acoplada, como também das etapas promovidas pela UBS. Os danos foram avaliados visualmente e analisados em um delineamento estatístico inteiramente casualizado, com os tratamentos distribuídos em esquema fatorial. A variedade Cruzeta foi mais resistente aos impactos provocados pela debulha e pelo beneficiamento; o efeito do impacto na qualidade das sementes torna-se mais evidente com a elevação da velocidade do cilindro debulhador; a rotação de 600 rpm mostrou-se a mais indicada para a debulha do milho Cruzeta e Sertanejo.<br>In the State of Paraiba, the loss of seeds and grains of corn (Zea mays L.) caused, mainly by harvesting, mechanical thrashing and subsequent processes is about 20% resulting in economic loss to the state. In this context, the effect of mechanical damages during the thrashing and passage of corn seeds varieties -Cruzeta- and -Sertanejo- were studied, in the different stages of processing. To evaluate the damages caused to the seeds, a stationary thrasher was used working at 520, 600 and 700 rpm, obtained by the acceleration variation of the tractor to which the thrasher was attached. The damages were visually appraised and analysed in a completely randomized statistical design with the treatments distributed in a factorial scheme. -Cruzeta- variety was more resistant to the impacts caused by the thrashing and processing; the impacts on the seed quality became more evident with the elevation of speed of the thrashing cylinder; the 600 rpm rotation proved to be better for the thashing of Cruzeta and Sertanejo corn