Complexos imínicos de cobre com atividade antiparasitária frente à doença de chagas / Imine copper complexes with antiparasitic activity against Chagas disease

Neste trabalho foram sintetizados e caracterizados três complexos de cobre com ligantes imínicos, com o objetivo de avaliar sua atividade tripanocida. Esses complexos foram caracterizados por diversas técnicas espectroscópicas, como UV-Vis, Infravermelho e EPR, além de análise elementar e espectrometria de massa. Juntamente com outros complexos similares previamente sintetizados pelo nosso grupo, tiveram suas atividades avaliadas frente à forma tripomastigota do parasita T. cruzi, responsável pela fase aguda da doença de Chagas, por ensaios de viabilidade celular, com determinação do valor de seus IC50, concentração em que observamos a morte de 50% da cultura celular, pela metodologia denominada MTT. Todos os complexos mostraram-se eficientes frente a tripomastigotas, apresentando valores de IC50 abaixo de 10 µM, com quatro deles obtendo índice de seletividade maior que 10, fator importante para definir agentes promissores antichagásicos. Complexos selecionados também tiveram sua atividade verificada frente à forma amastigota do parasita, responsável pela fase crônica da doença, utilizando método de imageamento por microscópio de fluorescência e contagem celular. Estudos de inibição da cruzaína, uma cisteíno-protease importante para o metabolismo do parasita foram conduzidos em colaboração com o laboratório do Prof. Wagner Alves de Souza Júdice, da Universidade de Mogi das Cruzes. Quatro dos compostos testados apresentaram atividade inibitória frente a cruzaína, sendo dois de cobre, um de zinco e um ligante livre. Os estudos também permitiram diferenciar os mecanismos de inibição dos compostos, com os complexos de cobre apresentando um mecanismo de inibição clássico e o composto de zinco e o ligante livre apresentando o mecanismo de inibição competitiva parabólica com cooperatividade

In this work, three copper complexes with iminic ligands were synthesized and characterized, with the objective of evaluating their trypanocidal activity. These complexes were characterized by several spectroscopic techniques, such as UV-Vis, Infrared and EPR, in addition to elementary analysis and mass spectrometry. Together with other similar complexes previously synthesized by our group, their activities were evaluated against the trypomastigote form of the parasite T. cruzi, responsible for the acute phase of Chagas disease, by cell viability tests, with determination of the value of their IC50, concentration in that we observed the death of 50% of the cell culture, by the methodology called MTT, all presenting IC50 values below 10 µM, with four of them obtaining a selectivity index greater than 10, important factor for defining promising antichagasic agents. Selected complexes also had their activity verified against the amastigote form of the parasite, responsible for the chronic phase of the disease, using a fluorescence microscope and cell counting imaging method. Inhibition studies of cruzain, a cysteine protease important for the metabolism of the parasite, were conducted in collaboration with the laboratory of Professor Wagner Alves de Souza Júdice at the University of Mogi das Cruzes. Four of the tested compounds showed inhibitory activity against cruzain, two of copper, one of zinc and a free ligand. The studies also allowed to differentiate the mechanisms of inhibition of the compounds, with the copper complexes presenting a classic inhibition mechanism and the zinc compound and the free ligand presenting the competitive parabolic inhibition mechanism with cooperativity

Síntese e funcionalização de compostos organoenxofre: sulfóxidos, sulfetos e N-sulfinil iminas / Synthesis and functionalization of organosulfur compounds: sulfoxides, sulfides and N-sulfinyl imines

Neste trabalho promovemos a síntese de sulfóxidos vinílicos ?-substituídos através da reação de acoplamento cruzado de Suzuki-Miyaura. Também foi feita a síntese de sulfóxidos enínicos inéditos, pela adição do nucleófilo no carbono ß-sulfóxido. Esses compostos eram passíveis de serem submetidos a reação de rearranjo de Pummerer aditivo e assim gerarem uma pequena biblioteca de compostos α-tioaldeídos. Um desses aldeídos sintetizados foi empregado na reação de formação de uma imina propargílica, com consequente reação de CuAAC formando iminas triazólicas. Outras iminas arílicas foram sintetizadas, passando por uma etapa de redução, com intuito de se obter a amina livre, para que fosse feita a reação de ciclização com auxílio de um agente eletrofílico. Outra classe de composto organoenxofre foi sintetizada, as N-sulfinil imina, que após a reação de acoplamento cruzado de Sonogashira, com consequente remoção de um grupo protetor e a formação do anel heterocíclico, foram obtidos compostos triazólicos N-sulfinil imínicos.

In this work we promote the synthesis of α-substituted vinylic sulfoxides through the Suzuki-Miyaura cross coupling reaction. Also the synthesis of unpublished enynic sulfoxides was made, by the addition of the nucleophile in the ß-sulfoxide carbon. These compounds were susceptible to additive Pummerer rearragement reaction and thus generated a small library of compounds. One of these aldehydes synthesized was used in the formation reaction of a propargyl imine, with consequent CuAAC reaction, forming triazol imines. Other aryl imines were synthesized, undergoing a reduction step, in order to obtain the free amine, so that the cyclization reaction was carried out with the aid of an electrophilic agent. Another class of organosulfur compound was synthesized, the N-sulfinyl imine, which after the Sonogashira cross-coupling reaction, with consequent removal of a protecting group and formation of the heterocyclic ring, N-sulfinyl imine triazolic compounds were obtained.

Antidote for acetaminophen poisoning: N-acetylcysteine

N-acetylcysteine (NAC) is widely recognized as the antidote of choice for acetaminophen overdose. Acetaminophen is a commonly used analgesic and antipyretic agent, and its use is one of the most common causes of poisoning worldwide. Acetaminophen toxicity may occur acutely when supratherapeutic amounts are ingested purposefully or unintentionally. Liver failure may occur in severe toxicity. However, if treated early, patients with acetaminophen poisoning generally recover uneventfully. Acetaminophen is metabolized to N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified by conjugation with glutathione. In overdose, hepatic stores of glutathione are depleted and NAPQI binding to hepatocytes induces cell death and hepatic necrosis. NAC replenishes hepatic glutathione and may also act as a glutathione substitute, combining directly with the toxic metabolite. Intravenous NAC is indicated in patients who present with a history of acetaminophen overdose within the previous 8 to 10 hours, patients unable to tolerate oral NAC, and patients who present with evidence of fulminant hepatic failure. However, caution should be used in patients who have experienced previous hypersensitivity or anaphylactoid reactions to intravenous NAC, as well as in patients with asthma. The most common anaphylactoid reactions include rash, flushing, and bronchospasm. Adults should receive 150 mg/kg administered for 45 minutes, followed by 50 mg/kg administered for 4 hours, followed by 100 mg/kg administered for 16 hours. The total dose is 300 mg/kg delivered over 21 hours. Additionally, caution should always be used when intravenous NAC is prescribed and the amount of diluent is calculated. Monitoring of patients with a should include repeated neurologic and hemodynamic assessment.

Facile construction of substituted pyrimido[4,5-d] pyrimidones by transformation of enaminouracil

The reaction of 6-amino-1,3-dimethylpyrimidine-2,4[1H,3H]-dione [1] as a binucleophile with primary aromatic or heterocyclic amines and formaldehyde or aromatic [heterocyclic] aldehydes in a molar ratio [1:1:2] gave the pyrimido[4,5-d]pyrimidin-2,4-dione ring systems 2-5. Treatment of 1 with diamines and formalin in molar ratio [2:1:4] gave the bis-pyrimido[4,5-d]pyrimidin- 2,4-diones 6-8. Furthermore, substituted pyrimido[4,5-d]pyrimidin-2,4-diones with uracil derivative 11 or spiro indole 16 were synthesized. Synthesis of pyrimido[4,5-d]pyrimidin-2,4-diones with different substitution at C-5 and C-7 was achieved to give 13 and 18, respectively

Expression of cytokeratin 10, 16 and 17 as biomarkers differentiating odontogenic keratocysts from dentigerous cysts

OBJECTIVES: Odontogenic keratocysts (OKCs) have a tendency to recur and possess an aggressive nature. the aim of the present study was to evaluate cytokeratin (CK) expression patterns as a method for the differentiation between dentigerous cysts (DCs) and OKCs, as their histomorphologic appearance are often indistinguishable. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissue sections of 43 OKCs and 38 DCs were immunohistochemically analyzed with i-solution in a quantitative manner in order to evaluate the immunoreactivity of CK 10, 16 and 17. RESULTS: CK 10 expression was evident in 79.1% of OKCs but found in only 18.4% of DCs (P<0.05), and CK 10 expression was observed to occur more frequently in OKCs (mean 25.45%) than in DCs (2.19%) (P<0.05). The expression of CK 16 was evident in 79.1% of OKCs but found in only 7.9% of the DCs (P<0.05) and CK 16 expression was observed to occur more frequently in OKCs (mean 4.33%) than in the DCs (0.61%) (P<0.05). The expression of CK 17 was evident in 88.4% of OKCs but seen in only 15.7% of the DCs (P<0.05) and CK 17 expression was observed to occur more frequently in OKCs (mean 31.11%) than in the DCs (2.37%) (P<0.05). CONCLUSION: The immunohistochemical detection of CK 10, 16 and 17 can be utilized as a valuable biomarker for use in distinguishing between OKCs and DCs, which have clinically significant differential diagnoses.

Current status of non-viral vectors for siRNA delivery / 药学学报

RNA interference (RNAi) is a newly developed technology. It is the different levels of gene silencing induced by specific degradation of targeted genes in vivo, and both exogenous and endogenous double-stranded RNAs could induce the specific degradation. RNAi has been applied in tumor therapy, viral infection, hepatitis B and many other diseases. siRNA is the effector molecule which induces the RNAi in vivo. But naked siRNA is easily degradated by RNases in vivo, and the half-life is short. Meanwhile, the transfection efficiency of the naked siRNA is comparatively low. So the naked siRNA needs the help of vectors to penetrate the cell membrane and take action. Viral vectors have the potential immunogenicity and mutagenicity in gene therapy. Therefore, non-viral vectors are drawing more and more attention. The latest development of the non-viral vectors is summarized in this review.

Two new phenolic acids from Drynariae rhizoma / 药学学报

To study the chemical constituents of Drynariae Rhizoma, nine phenolic acids were isolated from a 70% ethanol extract by using a combination of various chromatographic techniques including column chromatography over silica gel, ODS, Sephadex LH-20, and semi-preparative HPLC. By spectroscopic techniques including 1H NMR, 13C NMR, 2D NMR, and HR-ESI-MS, these compounds were identified as 4, 4'-dihydroxy-3, 3'-imino-di-benzoic acid (1), protocatechuic acid (2), gallic acid (3), p-hydroxybenzoic acid (4), (E)-caffeic acid (5), ethyl trans-3, 4-dihydroxycinnamate (6), caffeic acid 4-O-beta-D-glucopyranoside (7), p-coumaric acid 4-O-beta-D-glucopyranoside (8), and 23(S)-12-O-caffeoyl-12-hydroxyllauric acid glycerol ester (9), separately. Among them, 1 and 9 are new compounds, and 3, 4, and 6 were isolated from Drynaria species for the first time.

Role of inducible nitric oxide synthase on the development of virus-associated asthma exacerbation which is dependent on Th1 and Th17 cell responses

Asthma is characterized by airway inflammation induced by immune dysfunction to inhaled antigens. Although respiratory viral infections are the most common cause of asthma exacerbation, immunologic mechanisms underlying virus-associated asthma exacerbation are controversial. Clinical evidence indicates that nitric oxide (NO) levels in exhaled air are increased in exacerbated asthma patients compared to stable patients. Here, we evaluated the immunologic mechanisms and the role of NO synthases (NOSs) in the development of virus-associated asthma exacerbation. A murine model of virus-associated asthma exacerbation was established using intranasal challenge with ovalbumin (OVA) plus dsRNA for 4 weeks in mice sensitized with OVA plus dsRNA. Lung infiltration of inflammatory cells, especially neutrophils, was increased by repeated challenge with OVA plus dsRNA, as compared to OVA alone. The neutrophilic inflammation enhanced by dsRNA was partly abolished in the absence of IFN-gamma or IL-17 gene expression, whereas unaffected in the absence of IL-13. In terms of the roles of NOSs, dsRNA-enhanced neutrophilic inflammation was significantly decreased in inducible NOS (iNOS)-deficient mice compared to wild type controls; in addition, this phenotype was inhibited by treatment with a non-specific NOS inhibitor (L-NAME) or an specific inhibitor (1400 W), but not with a specific endothelial NOS inhibitor (AP-CAV peptide). Taken together, these findings suggest that iNOS pathway is important in the development of virus-associated exacerbation of neutrophilic inflammation, which is dependent on both Th1 and Th17 cell responses.

new spectrophotometric method for the determination of methyldopa

A new, simple and low cost spectrophotometric method for the determination of methyldopa in pharmaceutical preparations was developed. The method was based on the coupling of methyldopa with 2,6-dichloroquinone-4-chlorimide [DCQ]. The absorbance maximum [lambda max] of the resulted colored product was at 400nm. Different buffers were used to determine the optimal pH for the reaction. 1% w/v acetate buffer with pH 8.0 gave the optimal pH required for the reaction. Of the different solvents tried, water and ethanol were found to be the most suitable solvents. Beer's law was obeyed in concentration range of 4-20 micro g/ml methyldopa. The correlation coefficient was found to be [r=0.9975]. The limit of detection and limit of quantification were 1.1 micro g/ml and 3.21 micro g/ml, respectively. The reaction ratio between methyldopa and DCQ was studied and found to be 1:3. The work included the study of the possible interference of hydrochlorothiazide found in combination with methyldopa tablets. The method was validated and results obtained for the assay of two different brands of methyldopa tablets were compared with the B.P. method [colorimetric]. The repeatability and reproducibility of the developed method were evaluated and the obtained results quoted. The derivative formed as a result of the reaction of methyldopa with DCQ was isolated and its possible mechanistic pathway was suggested

LYR71, a derivative of trimeric resveratrol, inhibits tumorigenesis by blocking STAT3-mediated matrix metalloproteinase 9 expression

Tumor migration/invasion is the main cause of tumor progression and STAT3 is needed to enhance tumor migration/invasion by up-regulating MMP-9. Thus, agents that inhibit STAT3 activation may be used as an anticancer drug. We present herein that 6-methyl-2-propylimino-6, 7-dihydro-5H-benzo [1, 3]-oxathiol- 4-one (LYR71) , a derivative of trimeric resveratrol, has an anticancer activity through inhibition of STAT3 activation. We found that LYR71 suppressed STAT3 activation and inhibited the expression and activity of MMP-9 in RANTES-stimulated breast cancer cells. In addition, LYR71 reduced RANTES-induced MMP-9 transcripts by blocking STAT3 recruitment, dissociating p300 and deacetylating histone H3 and H4 on the MMP-9 promoter. Furthermore, LYR71 inhibited tumor migration/invasion in RANTES-treated breast cancer cells and consequently blocked tumor progression in tumor-bearing mice. Taken together, the results of this study suggest that LYR71 can be therapeutically useful due to the inhibition effect of STAT3-mediated MMP-9 expression in breast cancer cells.

Synthesis of new gene-loaded microbubbles serve as gene delivery vehicle applied in reporter gene transfer into cardiac myocytes / 生物医学工程学杂志

To improve the stability and gene-carried capability of gene-attached microbubbles, the method for manufacture of albumin microbubbles was modified and new gene-loaded microbubbles were synthesized by incorporated gene-PEI complex into the shell of microbubbles. Agarose gel electrophoresis and bacteria transformation showed that PEI had the ability to provide the protection of plasmid DNA from ultrasonic degradation. The new gene-loaded microbubbles exhibited excellent acoustical and hemorheological properties. Moreover, they could carry more plasmid DNA than gene-attached microbubbles. beta-galactosidase plasmid transfection into cardiac myocytes was performed by using ultrasound targeted destruction of new gene-loaded microbubbles or gene-attached microbubbles. Gene expression in cardiac myocytes was detected by beta-galactosidase in situ staining and quantitive assay. It was shown that beta-galactosidase activity in cardiac myocytes was enhanced 107-fold by ultrasonic destruction of gene-loaded microbubbles compared with naked plasmid transfection and new gene-loaded microbubbles resulted in 6.85-fold increase in beta-galactosidase activity compared with optimal transfection mediated by gene-attached microbubbles. These results suggested that ultrasonic destruction of the gene-loaded microbubbles can enhance the cardiac myocytes exogenous gene transfer efficiency significantly and new gene-loaded microbubbles is an efficient and safe gene delivery vehicle.

PEI-PMMA cationic nanoparticles as carriers for gene transfer / 药学学报

<p><b>AIM</b>To investigate the properties of cationic nanoparticles composed of poly (ethyleneimine)-g-poly (methyl methacrylate) (PEI-PMMA) as gene delivery carriers and explore the mechanism of PEI-PMMA nanoparticles mediated gene transfer.</p><p><b>METHODS</b>PEI-PMMA nanoparticles were synthesized by free radical polymerization. The morphology of nanoparticles was observed by scanning electron microscopy. The particle size and zeta potential were measured by zeta sizer. The complex between pGL3 plasmid and nanoparticles was analyzed by gel electrophoresis; and PEI-PMMA nanoparticles mediated gene transfer into HeLa cells was observed by confocal laser scanning microscopy.</p><p><b>RESULTS</b>PEI-PMMA nanoparticles are spherical shape and monodispersity. The particle size and zeta potential are 172 nm and +50.3 mV, respectively. When pGL3 plasmid complexed with nanoparticles at N/P ratio of 5: 1 and 20: 1, the particle size of pGL3/nanoparticle complex are 133 and 139 nm and zeta potential is + 21.4 and + 33.7 mV, respectively. pGL3 plasmid complexed with nanoparticles completely at N/P ratio of 5: 1. PEI-PMMA nanoparticles can deliver pGL3 plasmid into HeLa cells by endocytosis and release pGL3 into the cytosol.</p><p><b>CONCLUSION</b>PEI-PMMA nanoparticles effectively transferred DNA to target cells and it is a promising non-viral carrier for gene delivery.</p>

Synthesis of 4-, 6- or 7-substituted phenyliminomethylenecoumarins and their anticancer activities / 药学学报

<p><b>AIM</b>A series of substituted phenyliminomethylenecoumarins derivatives was designed in order to find compounds possessing anticancer activities.</p><p><b>METHODS</b>Title compounds (1a-b, 2a-b and 3a-q) were synthesized and screened by several anticancer models in vitro.</p><p><b>RESULTS</b>Twenty-one new compounds (1a-b, 2a-b and 3a-q) were synthesized and screened. Structures of the new compunds were determined by MS, HNMR and elemental analysis. Twelve compounds (3c, 3d, 3e, 3f, 3g, 3h, 3j, 3k, 3m, 3o, 3p, 3q) showed inhibitory effects on HCT-8, KB and Bel7402 cell lines in vitro.</p><p><b>CONCLUSION</b>Some compounds had certain anticancer activities and were worth further studying.</p>

Nickel [ll] and copper [ll] chelates of 1,2 diphenyl-1-oximino-2-n- [o-aminophenylaldimino] -ethanediylene and their reaction with acetylacetone and isonitrosoacetylacetone

Condensation of a-benzilmonoxime with o-phenylenediamine forms 1,2-dipherryl-1-oximino-2-N-[o-aminophenylafdimino]-ethanediyiene. Nickel [II] and copper [II] complexes of this imine-oxime are characterized. Linkage-isomerization of N- and O-oximato is explored. Phenyl side groups hinder impact of surroundings. In the acetate derivatives, the imine-oxime is deprotonated, and mass spectra exhibit base lines of dimers. O-oximato holds nickel [ln acetate dieter, while acetate links that of copper [Il]. Infrared spectra, magnetic and electrochemical behaviors support the dimerization- b-diketone such as acetyl-acetone or isonitrosoacetylacetone substitutes the acetate group. Replacement of the bridging acetate of the copper [II] chelate is accompanied by condensation between the carbonyl of diketonate and the amino group. Correlations between infrared frequencies and reduction potentials are used to identify the redox species. Unlike Ni[II]-chelates, -electron delocalization are expected within the ligand of the Cu[II]-chelates

Hydrazidoy halides in heterocyclic synthesis: Synthesis of several new polyfunctional pyrazole and 1,2,4-Triazole derivatives via dipolar cycloduction reactions on the corresponding nitrile imines

The nitrile imine generated by the action of triethylamine on 2-bromo-1-benzofurylglyoxal-2-[3 phenylpyrazol 5-yl]-hydrazone reacted with some Schiff bases, -nitrostyrenes and thiocarboxamidocinnamonitrile derivatives via dipolar cycloaddition reactions to yield several new polyfunctional pyrazole and 1,2,4-triazole derivatives. Structures were confirmed by elemental analysis and spectral data studies

Hydrazidoyl halides in heterocyclic synthesis.III+: synthesis of several new pyrazole pyrrolino [3,4-c] pyrazoles and pyrazolo [3,4-d] pyridazine, derivatives via dipolar cycloaddition reactions

A variety of new pyrazole, pyrrolinopyrazole and pyrazolopyridazine derivatives were synthesised via the dipolar cycloaddition reactions of acrylonitrile, ethyl acrylate and N-arylmaleimides with the nitrile imine regenerated from 2-bromo-1- benzofurylglyoxal-2-[3-phenylpyrazol-5-yl]-hydrazone. Structure of the newly synthesized derivatives were established on the basis of elemental analysis and spectral data

Preparacao e analise estrutural de iminas derivadas de dextranos oxidados e antimalaricos / Preparation and structural analysis derivative imines of oxidized dextrans and antimalarial

Com o objetivo de obter pro-farmacos potencialmente ativos em malaria, especialmente em malaria resistente, preparam-se, empregando-se o metodo da latenciacao, derivados de dextranos oxidados--MM 60.000-90.000, 70.000 e 500.000 -- com agentes antimalaricos. Sintetizaram-se iminas derivadas dos polimeros oxidados contendo um unico farmaco -- sulfas, sulfona -- e em associacao -- sulfas ou sulfona, e pirimetamina. Os compostos obtidos foram submetidos as analises espectrometricas no IV, UV de 'ANTPOT. 1'H RMN e de 'ANTPOT. 13'C RMN. Essas analises indicaram que os compostos que seguem foram obtidos: dextrano oxidado I (DOI) e dapsona (63), sulfadiazina (64), sulfametoxidiazina (65); dextrano oxidado II (DOII) e dapsona (67), sulfametoxazol, pH 6,0(71), sulfametoxipirida (72), sulfamonometoxina (73), dextrano oxidado III (DOIII) e dapsona (75), dextrano oxidado MM 70.000 (T70III) e sulfisoxazol); derivados de dextrano oxidado I (DOI) em associacao de pirimetamina e dapsona 1:1(91), de dextrano oxidado III em associacao de pirimetamina e dapsona, proporcao equimolar(95), de dextrano oxidado MM 70.000 (T70III) em associacao de pirimetamina e sulfametoxidiazina (99), de dextrano oxidado MM 70.000 (T70III) em associacao de pirimetamina e sulfametoxipiridazina (100) e ), de dextrano oxidado MM 500.000 (T500III) em associacao de pirimetamina e sulfametoxipiridazina (107). Com o objetivo de quantificar o farmaco no pro-farmaco, efetuaram-se analises quantitativas no UV com DOIDDS (63), DOISDZ (64), DOISMDZ (65), DOIISDX (69), DOIISMXZ pH 4,2 (70); DOIISMXZ pH 6,0 (71), DOIISMMX (73) e T70IIISFSXZ (80) mostraram graus de substituicao diversos. Dois desses compostos --derivados de dapsona e de sulfadiazina, foram submetidos a ensaios de liberacao in vitro, em valores diferentes de pH, apresentaram liberacao prolongada

Influencia de naftoquinona-iminas sobre la producción de peróxido de hidrógeno por Crithidia fasciculata y Leptomonas seymouri / Effect of naphthoquinone-imines on the production of hydrogen peroxide by Crithidia fasciculata and Leptomonas seymouri

Se ensayaron varias aminoisoxazolil-1,2-naftoquinomas sobre la formación de anión superóxido (O2) y peróxido de hidrógeno (H2O2) por Crithidia fasciculata y Leptomonas seymouri. Los compuestos IVD (N-(5-metil-3-isoxazolil)-4 amino-1,2-naftoquinona; IIID (2-hidroxi-N-(5-metil-3-isoxazoli)-1,4-naftoquinona-4-imina) y IIIE (2-hidroxi-N-(3-metil-5-isoxazolil)-1,4-naftoquinona-4-imina) estimularon la produción de H2O2 mientras que IIIE, IIIC (2-hidroxi-N-(3,5-dimetil-4-isoxazoli)-1,4-naftoquinona-4-imina) y IIIA (2-hidroxi-N-3,4-dimetil-5-isoxazolil)-1,4-naftoquinona-4-imina), pero no IVD, estimularon la formación de O2 en los organismos estudiados. El ciclo redox de las quinona-iminas se verificó por a) la variación de su absorbancia en función de la concentración de oxígeno en el medio de suspensión de las células; b) su reducción anaeróbica, relativamente rápida, con velocidad máxima para IVD; c) la oxidación de los quinoles correspondientes, obtenidos por reducción con borohidruro. C. fasciculata y L. seymouri contenían superóxido dismutasa, enzima esencial para la formación de peróxidos como consecuencia del ciclo redox de las quinonas, y también catalasa, cuya actividad fue seis veces mayor en C. fasciculata. La presencia de catalasa no impidió la formación de H2O2, como producto metabólico de las quinona-iminas. No se pudo demostrar actividad de ascorbato peroxidasa, benzidina peroxidasa o guayacol peroxidasa en los organismos estudiados

Inhibición del crecimiento y la síntesis de DNA y formación de anión superóxido por quinona-iminas en Trypanosoma cruzi / Quinone-imine inhibition of growth and DNA synthesis, and induction of superoxide anion generation in Trypanosoma cruzi

Se ensayaron cuatro aminodisoxazolil -1, 2, -naftoquinosa sobre el crecimiento, la síntesis de DNA y la producción de anión superóxido por Trypanosoma cruzi. Las quinona-iminas a) inhibieron el crecimiento y la síntesis de DNA; b) aumentaron el consumo de oxígeno de los epimastigotes y c) estimularon la formación de anión superóxido por los epimastigotes enteros y las fracciones mitocondrial y microsomal. La antimicina, un inhibidor, un inhibidor del transporte de electrones mitocondrial, intensificó la acción de las quinona-iminas sobre la respiración y la formación de anión superóxido. Reacciones redox demostrables espectroscópicamente corroboraron la intervención de las quinoma-iminas en la producción de oxiradicales por T. cruzi