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Braz. J. Pharm. Sci. (Online) ; 55: e18087, 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1039044


Leishmaniasis is one of the neglected diseases that remain in need for pharmacological alternatives. In this context, N-Myristoyltransferases (NMT) arise as interesting targets to explore since they are involved in the co/post-translational processing of peptides which are responsible for host cell invasion. Studies that consider these enzymes as targets point out the potential of benzoheterocyclic compounds as inhibitors of Candida albicans's N-myristoyltransferase. Here we applied a combination of comparative binding site analysis and molecular docking studies based on a Piggyback approach in the search for new Leishmania major NMT ligands. Our results revealed that NMT enzymes from both pathogens present enough structural similarity to allow extrapolation of the knowledge available from C. albicans studies to develop new L. major NMT inhibitors. Molecular docking studies with benzoheterocyclic analogues indicate the potential of benzothiazole derivatives as L. major NMT ligands, giving rise to a completely new class of chemical compounds to be explored in the development of antileishmanial drugs.

Benzofuranos/farmacologia , Leishmaniose/tratamento farmacológico , Leishmania major , Candida albicans , Enzimas/análise
An. acad. bras. ciênc ; 89(2): 1073-1084, Apr.-June 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-886689


ABSTRACT This study aimed to evaluate the teratogenic and hepatotoxic potential of the usnic acid encapsulated into PLGA-microspheres. In total, 12 female Wistar rats in pregnancy were randomly distributed in the control group (n= 6) that received 1.0 mL of physiological solution and treatment group (n= 6) that received 25 mg/kg of encapsulated usnic acid by oral administration. All females were euthanized at day 20 of pregnancy and their fetuses were removed and analyzed. During the pregnancy was observed a reduction in weight gain. There was no difference in serum transaminases levels analyzed as well as any difference in liver weight in both groups. The histomorphometric analysis of the liver from the treatment group revealed an increase in number of hepatocytes and a decrease in nuclear area of these cells. Moreover, no alteration was observed in cell area of hepatocytes or number of Kupffer cells. The fetuses had an increase in total number of hepatocytes and a reduction in the amount of megakaryocytes. These results show the hepatotoxic potential of usnic acid during pregnancy. However, its toxicity can be minimized by encapsulation in microspheres.

Animais , Feminino , Gravidez , Ácido Poliglicólico/toxicidade , Ascomicetos/química , Benzofuranos/toxicidade , Ácido Láctico/toxicidade , Feto/efeitos dos fármacos , Líquens/química , Fígado/efeitos dos fármacos , Ácido Poliglicólico/química , Valores de Referência , Anormalidades Induzidas por Medicamentos , Benzofuranos/química , Distribuição Aleatória , Ratos Wistar , Exposição Materna , Ácido Láctico/química , Peso Fetal/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Fígado/patologia
Bol. latinoam. Caribe plantas med. aromát ; 16(1): 14-25, ene. 2017. graf, ilus
Artigo em Inglês | LILACS | ID: biblio-907561


The tree tomato (Solanum betaceum Cav., Solanaceae) anthracnose, caused by the fungi Colletotrichum acutatum and Colletotrichum gloeosporioides, is the most important disease of this crop in Colombia for its wide distribution and the losses it causes. In the present work, the in vitro antifungal activity of the soluble fractions in n-hexane, dichloromethane, and ethyl acetate, and their major constituents from the sawdust of timber specie Platymiscium gracile Benth. (Fabaceae) against both fungi was evaluated. The n-hexane-soluble fraction exhibited the greatest inhibitory effect. The metabolites homopterocarpin (a pterocarpan, 0.39 percent dry weight), calycosin (an isoflavone, 2.01 percent) and scoparone (a coumarin, 1.48 percent) were isolated for the first time from wood sawdust of P. gracile. The structure of these compounds was determined by 1H and 13C NMR analyses. The three compounds tested showed significant antifungal activity.

La antracnosis del tomate de árbol (Solanum betaceum Cav., Solanaceae), ocasionada por los hongos Colletotrichum acutatum y Colletotrichum gloeosporioides, es la enfermedad más importante de este cultivo en Colombia por su amplia distribución y las pérdidas que ocasiona. En el presente trabajo se evaluó la actividad antifúngica in vitro de las fracciones solubles en n-hexano, diclorometano y acetato de etilo, y sus componentes mayoritarios, del aserrín de la especie maderable Platymiscium gracile Benth. (Fabaceae), contra ambos hongos. La fracción en n-hexano exhibió el mayor efecto inhibitorio. Los metabolitos homopterocarpina (un pterocarpano; 0.39 por ciento del peso seco de aserrín), calicosin (una isoflavona; 2.01 por ciento) y escoparona (una cumarina; 1.48 por ciento) se aislaron por primera vez desde el aserrín de madera de P. gracile empleando técnicas cromatográficas. La estructura de los compuestos se determinó por análisis de RMN de 1H y 13C. Los tres metabolitos mostraron una actividad antifúngica significativa contra ambos hongos.

Antifúngicos/farmacologia , Colletotrichum , Fabaceae/química , Benzofuranos/farmacologia , Benzopiranos/farmacologia , Técnicas In Vitro , Isoflavonas/farmacologia , Testes de Sensibilidade Microbiana , Madeira
Braz. j. med. biol. res ; 50(6): e5954, 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-839306


Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250–300 g) were obtained and split into four groups with ten rats in each group. The right kidney of all rats was removed (nephrectomy). The rats of the Control group received only saline (occlusion) and served as a sham control group, whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left renal artery served as a postitive control group. The other 2 groups of rats were pretreated with SAB (20 and 40 mg·kg-1·day-1) for 7 days prior IR induction and served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr) and blood urea nitrogen (BUN) were significantly lower in the groups that received SAB. Pretreatment with SAB appears to attenuate oxidative stress by suppressing the production of lipid peroxidation products like malondialdehyde as well as elevating antioxidant activity. The concentration of inflammatory markers and neutrophil infiltration (myeloperoxidase) were significantly decreased. Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly upregulated upon supplementation with SAB, indicating its renoprotective activity. Taken together, these results indicate that SAB can therapeutically alleviate oxidative stress and inflammatory process via modulating PI3K/Akt signaling pathway and probably ameliorate renal function and thus act as a renoprotective agent.

Animais , Masculino , Benzofuranos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Nitrogênio da Ureia Sanguínea , Creatinina/metabolismo , Inflamação/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidase/efeitos dos fármacos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais
Mem. Inst. Oswaldo Cruz ; 111(5): 330-334, May 2016. tab
Artigo em Inglês | LILACS | ID: lil-782055


Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 µg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb.

Humanos , Antibióticos Antituberculose/farmacologia , Benzofuranos/farmacologia , Isoniazida/farmacologia , Lipossomos , Mycobacterium tuberculosis/efeitos dos fármacos , Rifampina/farmacologia , Cápsulas , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana
Rev. Soc. Bras. Med. Trop ; 48(1): 11-17, jan-feb/2015. tab, graf
Artigo em Inglês | LILACS, Sec. Est. Saúde SP | ID: lil-742966


INTRODUCTION : Brazilian spotted fever (BSF) is a disease transmitted by ticks for which the etiological agent is Rickettsia rickettsii. The present essay evaluates the risk factors associated with the transmission of cases of BSF in the time period between 2003 and 2013 in the Piracicaba river basin, state of São Paulo. METHODS : This essay presents a retrospective study to identify the factors associated with the transmission of cases of BSF among all suspected cases identified by the System for Epidemiological Surveillance of São Paulo (CVE). After the description of temporal distribution (onset of symptoms) and the environmental and demographic variations of the confirmed and discarded cases, a multiple logistic regression model was applied. RESULTS : We searched 569 probable locations of infection (PLI) with 210 (37%) confirmed cases of BSF and 359 (63%) discarded cases. The associated variables for the confirmation of BSF in the multiple logistic model using a confidence interval (CI) of 95% were age (OR = 1.025 CI: 1.015-1.035), the presence of Amblyomma sculptum in the environment (OR = 1.629 CI: 1.097-2.439), the collection of ticks from horses (OR = 1.939 CI: 0.999-3.764), the presence of capybaras (OR = 1.467 CI: 1.009-2.138), an urban environment (OR = 1.515 CI: 1.036-2.231), and the existence of a dirty pasture (OR = 1.759 CI: 1.028-3.003). CONCLUSIONS : The factors associated with the confirmation of BSF cases included an urban environment, age, presence of the A. sculptum vector, the collection of ticks from horses, the presence of a capybara population, and a dirty pasture environment. .

Animais , Masculino , Ratos , Apoptose/genética , Benzofuranos/uso terapêutico , Apoptose/efeitos dos fármacos , Western Blotting , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Eletroforese em Gel Bidimensional , Hemodinâmica/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Microscopia Eletrônica de Transmissão , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/citologia , Miocárdio/metabolismo , Miocárdio/ultraestrutura , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem
Mem. Inst. Oswaldo Cruz ; 110(1): 86-94, 03/02/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-741617


Trypanosoma cruzi strains from distinct geographic areas show differences in drug resistance and association between parasites genetic and treatment response has been observed. Considering that benznidazole (BZ) can reduce the parasite burden and tissues damage, even in not cured animals and individuals, the goal is to assess the drug response to BZ of T. cruzi II strains isolated from children of the Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected and treated with BZ in both phases of infection were compared with the untreated and evaluated by fresh blood examination, haemoculture, polymerase chain reaction, conventional (ELISA) and non-conventional (FC-ALTA) serologies. In mice treated in the acute phase, a significant decrease in parasitaemia was observed for all strains. Positive parasitological and/or serological tests in animals treated during the acute and chronic (95.1-100%) phases showed that most of the strains were BZ resistant. However, beneficial effect was demonstrated because significant reduction (p < 0.05%) and/or suppression of parasitaemia was observed in mice infected with all strains (acute phase), associated to reduction/elimination of inflammation and fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals, what suggest that BZ use may be recommended at least for recent chronic infection of the studied region.

Humanos , Descoberta de Drogas , Resíduos Industriais/análise , Nootrópicos/isolamento & purificação , Extratos Vegetais/química , Brotos de Planta/química , Estilbenos/isolamento & purificação , Vitis/química , Agricultura/economia , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Benzofuranos/análise , Benzofuranos/química , Benzofuranos/economia , Benzofuranos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , França , Resíduos Industriais/economia , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/economia , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Nootrópicos/química , Nootrópicos/economia , Nootrópicos/farmacologia , Agregação Patológica de Proteínas , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/metabolismo , Fenóis/química , Fenóis/economia , Extratos Vegetais/economia , Agregados Proteicos/efeitos dos fármacos , Espectrometria de Massas por Ionização por Electrospray , Estereoisomerismo , Estilbenos/análise , Estilbenos/química , Estilbenos/economia , Estilbenos/farmacologia
Bol. latinoam. Caribe plantas med. aromát ; 13(4): 375-380, jul. 2014. ilus, tab
Artigo em Inglês | LILACS | ID: lil-785455


Four 3H-spiro1-benzofuran-2, 1’-cyclohexanes were synthesized from filifolinol, two of which are reported for the first time. Docking molecular studies were carried out to determine in silico whether these derivatives have similar immunostimulant activity to that reported for filifolinol, and its oxidation product, filifolinone. Through of the study of interactions of these compounds with the heterodimer of the protein present in teleost TLR1-TLR2, filifolinol, 3’-filifolinchloride and filifolinyl acetate shows similar interactions between them, allowing to predict that they would have similar immunostimulant activity, but different to filifolinone and filifolinane or that they would act by a different mechanisms.

Cuatro 3H-spiro1-benzofuran-2, 1'-ciclohexanos se sintetizaron a partir de filifolinol, dos de los cuales son reportados por primera vez. Se llevaron a cabo estudios de docking molecular para determinar in silico si estos derivados tienen actividad inmunoestimulante similar a la reportada para filifolinol y su producto de oxidación, filifolinona. A través del estudio de las interacciones de estos compuestos con el heterodímero de la proteína presente en teleósteos TLR1-TLR2 se estableció que el filifolinol, 3'-cloruro de filifolinilo y acetato de filifolinilo tienen interacciones similares con el heterodímero, lo que permite predecir que entre ellos tendrían una actividad simi- lar, pero diferente a la de la filifolinona y filifolinano o que estos últimos actuarían por diferentes mecanismos.

Adjuvantes Imunológicos , Benzofuranos/química , Cicloexanos/química , Heliotropium , Compostos de Espiro/química , Modelos Moleculares , Receptores Toll-Like , Medicina Veterinária
Braz. j. med. biol. res ; 46(8): 643-649, ago. 2013. graf
Artigo em Inglês | LILACS | ID: lil-684525


MP [4-(3′,3′-dimethylallyloxy)-5-methyl-6-methoxyphthalide] was obtained from liquid culture of Pestalotiopsis photiniae isolated from the Chinese Podocarpaceae plant Podocarpus macrophyllus. MP significantly inhibited the proliferation of HeLa tumor cell lines. After treatment with MP, characteristic apoptotic features such as DNA fragmentation and chromatin condensation were observed in DAPI-stained HeLa cells. Flow cytometry showed that MP induced G1 cell cycle arrest and apoptosis in a dose-dependent manner. Western blotting and real-time reverse transcription-polymerase chain reaction were used to investigate protein and mRNA expression. MP caused significant cell cycle arrest by upregulating the cyclin-dependent kinase inhibitor p27KIP1 protein and p21CIP1 mRNA levels in HeLa cells. The expression of p73 protein was increased after treatment with various MP concentrations. mRNA expression of the cell cycle-related genes, p21CIP1 , p16INK4a and Gadd45α, was significantly upregulated and mRNA levels demonstrated significantly increased translation of p73, JunB, FKHR, and Bim. The results indicate that MP may be a potential treatment for cervical cancer.

Humanos , Apoptose/efeitos dos fármacos , Benzofuranos/administração & dosagem , Endófitos/química , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Xylariales/química , Proteínas Reguladoras de Apoptose/genética , Benzofuranos/isolamento & purificação , Proteínas de Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , /efeitos dos fármacos , /efeitos dos fármacos , Proteínas de Ligação a DNA/efeitos dos fármacos , Citometria de Fluxo , Fatores de Transcrição Forkhead/efeitos dos fármacos , Cycadopsida , /efeitos dos fármacos , Células HeLa , Proteínas Nucleares/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Transcrição Genética , Fatores de Transcrição/efeitos dos fármacos , Proteínas Supressoras de Tumor/efeitos dos fármacos
Braz. j. med. biol. res ; 45(5): 401-407, May 2012. ilus
Artigo em Inglês | LILACS | ID: lil-622769


The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of Parkinson’s disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.

Animais , Ratos , /toxicidade , Autofagia/efeitos dos fármacos , Benzofuranos/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson Secundária/patologia , Apium/química , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Imuno-Histoquímica , Microscopia Eletrônica de Transmissão , Doença de Parkinson Secundária/induzido quimicamente , Sementes/química
Bol. latinoam. Caribe plantas med. aromát ; 11(3): 285-290, mayo 2012. ilus
Artigo em Inglês | LILACS | ID: lil-647667


The in vitro effect of the 3 H-spiro [1-benzofuran-2,1’-ciclohexane] derivative (Filifolinone), was evaluated on mouse dendritic cells through the level of expression of MHC molecules class II by flow cytometry. The results show that Filifolinone increases the expression of MHC promoting maturation of dendritic cells. The results suggest that Filifolinone is a potential immunomodulator for veterinary use.

La actividad in vitro del derivado 3H-espiro [1-benzofurano-2,1’-ciclohexano] (Filifolinona), fue evaluado en células dendríticas de ratón a través del nivel de expresión de moléculas MHC clase II utilizando citometría de flujo. Los resultados muestran que Filifolinona incrementa la expresión de MHC promoviendo la maduración de las células dendríticas. Estos resultados permiten sugerir que Filifolinona es un potencial inmunomodulador de uso veterinario.

Animais , Feminino , Camundongos , Benzofuranos , Células Dendríticas , Heliotropium/química , Fatores Imunológicos , Compostos de Espiro , Citometria de Fluxo , Camundongos Endogâmicos BALB C
Bol. latinoam. Caribe plantas med. aromát ; 10(3): 281-288, mayo 2011. ilus, tab
Artigo em Inglês | LILACS | ID: lil-687017


The in vitro effect of the resinous exudate of Heliotropium filifolium, of the 3 H-spiro[1-benzofuran-2,1 '-cyclohexane] derivative called filifolinol 1, isolated from the resin and the semi-synthetic compounds filifolinone 2 and filifolinoic acid 3, obtained from filifolinol 1, were evaluated on the proliferation of an immortalized cell line, UCHT1, derived from rat thyroid. We evaluated the effect of these compounds on UCHT1 cell growth parameters by calculating doubling time; and toxicity using the LIVE/DEAD™ in vitro test. The results showed that the resin is not active, while filifolinone 2, filifolinoic acid 3 and filifolinol 1 produced a significant inhibition of cell doubling time, in concentrations equal or greater than 50, 25 and 75 uM, respectively. The LIVE/DEAD test showed no significant toxicity at these concentrations, compared to cultures kept in absence of compounds. These results suggest a possible cytostatic effect of these compounds, and could therefore constitute potential alternatives for antineoplasic therapy.

Se evaluó el efecto in vitro de la resina aislada desde Heliotropium filifolium y del derivado 3 H-spiro[1-benzofuran-2,1'-cyclohexano] llamado filifolinol 1, obtenido desde este exudado resinoso y los compuestos semi-sintéticos filifolinona 2 y ácido filifolinoico 3, obtenidos a partir de filifolinol 1, sobre la proliferación de la línea celular inmortal, UCHT1, derivada de tumor de tiroide de rata. Evaluamos el efecto de estos compuestos en el desarrollo celular de UCHT1 a través de los parámetros tiempo de doblaje y citotoxicidad usando el test LIVE/DEAD™ in vitro. Los resultados mostraron que la resina no presentó actividad y que filifolinona, ácido filifolinoico y filifolinol producen una inhibición significativa del tiempo de doblaje celular, en concentraciones iguales o superiores a 50, 25 y 75 uM, respectivamente. El test LIVE/DEAD no mostró toxicidad significativa en comparación con los cultivos mantenidos en ausencia de compuestos. Estos resultados sugieren un posible efecto citostático de estos compuestos y por lo tanto, constituirían alternativas potenciales para terapia antineoplásica.

Animais , Ratos , Antineoplásicos/farmacologia , Extratos Vegetais/farmacologia , Heliotropium/química , Neoplasias da Glândula Tireoide/tratamento farmacológico , Proliferação de Células , Benzofuranos , Cicloexanos , Exsudatos de Plantas/farmacologia , Resinas Vegetais , Compostos de Espiro , Sobrevivência Celular , Técnicas de Cultura de Tecidos
Braz. j. biol ; 70(3): 659-664, Aug. 2010. ilus, tab
Artigo em Inglês | LILACS | ID: lil-555287


Usnic acid, a lichen metabolite, is known to exert antimitotic and antiproliferative activities against normal and malignant human cells. Many chemotherapy agents exert their activities by blocking cell cycle progression, inducing cell death through apoptosis. Microtubules, protein structure involved in the segregation of chromosomes during mitosis, serve as chemotherapeutical targets due to their key role in cellular division as well as apoptosis. The aim of this work was to investigate whether usnic acid affects the formation and/or stabilisation of microtubules by visualising microtubules and determining mitotic indices after treatment. The breast cancer cell line MCF7 and the lung cancer cell line H1299 were treated with usnic acid 29 µM for 24 hours and two positive controls: vincristine (which prevents the formation of microtubules) or taxol (which stabilizes microtubules). Treatment of MCF7 and H1299 cells with usnic acid did not result in any morphological changes in microtubules or increase in the mitotic index. These results suggest that the antineoplastic activity of usnic acid is not related to alterations in the formation and/or stabilisation of microtubules.

O ácido úsnico, um metabólito de liquens, é conhecido por sua atividade antimitótica e antiproliferativa em células humanas normais e malignas. Muitos quimioterápicos exercem suas atividades bloqueando a progressão do ciclo celular e induzindo morte celular por apoptose. Os microtúbulos, estruturas protéicas envolvidas na segregação dos cromossomos durante a mitose, servem como alvo quimioterapêutico devido ao seu importante papel tanto na divisão celular quanto nos mecanismos de morte celular por apoptose. O objetivo deste trabalho foi investigar se o ácido úsnico afeta a formação e/ou estabilização dos microtúbulos, a partir da visualização de microtúbulos e determinação de índices mitóticos após o tratamento. Células de câncer de mama MCF7 e de câncer de pulmão H1299 foram tratadas por 24 horas com 29 µM de ácido úsnico e dois controles positivos: vincristina (que impede a formação de microtúbulos) e taxol (que estabiliza microtúbulos). O tratamento das células MCF7 e H1299 com o ácido úsnico não resultou em aumento do índice mitótico. Os resultados sugerem que a atividade antineoplásica do ácido úsnico não está relacionada a alterações na formação e/ou estabilização de microtúbulos.

Feminino , Humanos , Antimitóticos/farmacologia , Antineoplásicos/farmacologia , Benzofuranos/farmacologia , Microtúbulos/efeitos dos fármacos , Paclitaxel/farmacologia , Vincristina/farmacologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral/efeitos dos fármacos , Neoplasias Pulmonares/patologia
Acta bioquím. clín. latinoam ; 39(1): 27-36, mar.2005. tab, graf
Artigo em Espanhol | LILACS | ID: lil-508376


El objetivo del presente trabajo fue investigar los efectos de la anestesia con Enflurano e Isoflurano en ratones con niveles hepáticos de citocromo P-450 (CYP) disminuidos o aumentados. Los animales previamente tratados con alilisopropil-acetamida(AIA) (350 mg/Kg), agente destructor del CYP o con Imidazol (400 mg/Kg) como inductor, recibieron una única dosis de los anestésicos ( 1mL/Kg). En el grupo que recibió AIA, los niveles de CYP permanecieron reducidos aún después de la anestesia. Sin embargo, los anestésicos revirtieron el aumento del CYP provocado por Imidazol. La actividad de la isoforma CYP2E1 se indujo en los grupos que recibieron los anestésicos, siendo mayor por la acción conjunta de imidazol y Enflurano, esto indicaría un aumento en la metabolización de este anestésico. En Animales tratados con Imidazol, el Isoflurano revirtió parcaialmente la inhibición de las actividades de B-glucuronidasa y sulfatasa producidas por dicho xenobiótico. Ambos anestésicos causaron una reducción en la actividad de triptofano pirrolasa en el grupo que recibió Imidazol pero no en los tratados con AIA. En conclusión, la acción de los anestésicos Enflurano e Isoflurano sobre el sistema metabolizante de drogas dependería de que el CYP esté inducido o no y del anestésico estudiado a pesar de su similitud estructural.

Humanos , Carcinógenos , Poluentes Ambientais , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Antracenos/efeitos adversos , Benzofuranos/efeitos adversos , Poluentes Químicos , Combustíveis Fósseis/efeitos adversos , Poluição Ambiental , Fenantrenos/efeitos adversos , Biomarcadores , Neoplasias/etiologia
Mem. Inst. Oswaldo Cruz ; 86(suppl. 2, n.esp): 25-9, Oct. 1991. ilus
Artigo em Inglês | LILACS | ID: lil-127824


A rational method of search for natural neolignans of desired structures is outlined. This involves consultation of a collection of chemical profiles of plant families. The profiles are assembledconsidering the biosynthetic class (in the present case lignoids), subclass (neolignans), structural types (neolignan skeleta) and relative frequency of substitutional derivatives belonging to each type (known compounds). The method is of course applicable to ani class of natural products. Its use in the case of neolignans is here selected as an exemple in view of the recently discovered antagonism towards PAF of kadsurenone, a representative of this subclass of phytochemicals. Application of the chemical profiles to phylogenetic studies is illustrated

Lignina/isolamento & purificação , Benzofuranos/química , Benzofuranos/isolamento & purificação , Benzofuranos/farmacologia , Desenho de Fármacos , Fator de Ativação de Plaquetas/antagonistas & inibidores , Lignina/química , Lignina/farmacologia , Estrutura Molecular , Plantas Medicinais/química
Rev. cuba. med ; 24(12): 1286-93, dic. 1985. tab
Artigo em Espanhol | LILACS | ID: lil-40054


Se utilizó la amiodarona en 80 pacientes con síntomas por taquiarritmias rebeldes. Fue efectiva en el 72,2% de los 44 pacientes con taquiarritmias supraventriculares y en el 86,1% de los que sufrían por arritmias ventriculares. Estos pacientes se siguieron durante 18 meses, aunque en 9 no se completó el tiempo de observación. El tiempo medio de comienzo de la efectividad de la droga fue de 7,5 días. Se sugiere que los microputeados en la córnea que comenzaron a detectarse a partir de los primeros 15 días del tratamiento pueden considerarse como un signo de impregnación del medicamento. Se recomienda el empleo de este fármaco en pacientes cuyo tratamiento con otras drogas antiarrítmicas haya fracasado, pues a pesar de su eficacia puede ocasionar diversas reacciones indeseables

Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Arritmias Cardíacas/tratamento farmacológico , Benzofuranos/uso terapêutico , Benzofuranos/efeitos adversos , Ensaios Clínicos como Assunto
Rev. cuba. med ; 24(11): 1199-208, nov. 1985. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-40085


Se indican los aspectos farmacoclínicos de la amiodarona y se revisan algunos aspectos que tienen vigencia en la práctica clínica diaria. Se informa el uso de la amiodarona como uno de los fármacos antiarrítmicos más importantes de la última década y los beneficios e inconvenientes que puede obtener un paciente con su uso

Humanos , Arritmias Cardíacas/tratamento farmacológico , Benzofuranos , Benzofuranos/administração & dosagem , Benzofuranos/farmacologia , Benzofuranos/toxicidade , Química