RESUMEN
Sepsis is characterized by a dysregulated immune response to infection characterized by an early hyperinflammatory and oxidative response followed by a subsequent immunosuppression phase. Although there have been some advances in the treatment of sepsis, mortality rates remain high, urging for the search of new therapies. ß-Lapachone (ß-Lap) is a natural compound obtained from Tabebuia avellanedae Lorentz ex Griseb. with several pharmacological properties including bactericidal, anti-inflammatory, and antioxidant activity. Thus, the aim of this study was to evaluate the effects of ß-Lap in a mouse sepsis model. To this, we tested two therapeutic protocols in mice submitted to cecal ligation and puncture- (CLP-) induced sepsis. First, we found that in pretreated animals, ß-Lap reduced the systemic inflammatory response and improved bacterial clearance and mouse survival. Moreover, ß-Lap also decreased lipid peroxidation and increased the total antioxidant capacity in the serum and peritoneal cavity of septic animals. In the model of severe sepsis, the posttreatment with ß-Lap was able to increase the survival of animals and maintain the antioxidant defense function. In conclusion, the ß-Lap was able to increase the survival of septic animals by a mechanism involving immunomodulatory and antioxidant protective effects.
Asunto(s)
Naftoquinonas/uso terapéutico , Sepsis/tratamiento farmacológico , Sepsis/mortalidad , Animales , Antiinflamatorios/uso terapéutico , Quimioprevención/métodos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Terapia de Inmunosupresión/métodos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/mortalidad , Mediadores de Inflamación/metabolismo , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Sepsis/metabolismo , Sepsis/patología , Tasa de SupervivenciaRESUMEN
BACKGROUND: Plasmodium falciparum has become resistant to some of the available drugs. Several plant species are used for the treatment of malaria, such as Himatanthus articulatus in parts of Brazil. The present paper reports the phyto-chemistry, the anti-plasmodial and anti-malarial activity, as well as the toxicity of H. articulatus. METHODS: Ethanol and dichloromethane extracts were obtained from the powder of stem barks of H. articulatus and later fractionated and analysed. The anti-plasmodial activity was assessed against a chloroquine resistant strain P. falciparum (W2) in vitro, whilst in vivo anti-malarial activity against Plasmodium berghei (ANKA strain) was tested in mice, evaluating the role of oxidative stress (total antioxidant capacity--TEAC; lipid peroxidation--TBARS, and nitrites and nitrates--NN). In addition, cytotoxicity was evaluated using the HepG2 A16 cell-line. The acute oral and sub-chronic toxicity of the ethanol extract were evaluated in both male and female mice. RESULTS: Plumieride was isolated from the ethyl acetate fraction of ethanol extract, Only the dichloromethane extract was active against clone W2. Nevertheless, both extracts reduced parasitaemia in P. berghei-infected mice. Besides, a significant reduction in pulmonary and cerebral levels of NN (nitrites and nitrates) was found, as well as in pulmonary TBARS, indicating a reduced oxidative damage to these organs. The ethanol extract showed low cytotoxicity to HepG2 A16 cells in the concentrations used. No significant changes were observed in the in vivo toxicity studies. CONCLUSIONS: The ethanol extract of H. articulatus proved to be promising as anti-malarial medicine and showed low toxicity.
Asunto(s)
Antimaláricos/farmacología , Antimaláricos/toxicidad , Apocynaceae/química , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Plasmodium berghei/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Animales , Antimaláricos/efectos adversos , Antimaláricos/aislamiento & purificación , Brasil , Línea Celular , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Malaria/tratamiento farmacológico , Masculino , Ratones , Parasitemia/tratamiento farmacológico , Corteza de la Planta/química , Extractos Vegetales/efectos adversos , Extractos Vegetales/aislamiento & purificación , Tallos de la Planta/química , Resultado del TratamientoRESUMEN
Chemical transformations of eremantholide C (1), a sesquiterpene lactone that was isolated from Lychnophora trichocarpha Spreng. led to five new derivatives: 1',2'- epoxyeremantholide C (2), 5-n-propylamine-4,5-dihydro-1',2'-epoxyeremantholide C (3), 5-n-propylammonium-4,5-dihydro-1',2'-epoxyeremantholide C chloride (4), 5-n-propylammonium-4,5-dihydroeremantolide C chloride (5) and 16-O-ethyleremantholide C (6). The structures of all these derivatives were assigned on the basis of IR, MS, 1H and 13C NMR data by 1D and 2D techniques. Eremantholide C and the derivatives 2, 4 and 5 were evaluated against trypomastigotes Y and CL strains of Trypanosoma cruzi. Eremantholide C completely inhibited the growth of both the parasites strains while all derivatives were partially active against the CL strain and inactive against the Y strain.
Asunto(s)
Asteraceae/química , Extractos Vegetales/farmacología , Sesquiterpenos/farmacología , Trypanosoma cruzi/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Parasitaria , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificaciónRESUMEN
Pectolinarin, a flavone heteroside, was isolated from Distictella elongata (Vahl) Urb. leaves ethanol extract, along with a mixture of ursolic, pomolic and oleanolic acids, besides ß-sitosterol. Their structures were established on the basis of spectral analysis (1H and 13C NMR, 1D and 2D) and they were compared with literature. This is the first report on the occurrence of this flavonoid in a species of the Bignoniaceae family.
Asunto(s)
Bignoniaceae/química , Flavonoides/química , Flavonoides/aislamiento & purificación , Hojas de la Planta/química , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia MagnéticaRESUMEN
The leaves of Mikania laevigata and Mikania glomerata are used in Brazil to treat respiratory affections, being kaurane-type diterpenes and coumarin considered as the bioactive compounds. The present study reports an investigation on the HPLC-DAD profiles and contents of coumarin (1), trans-o-coumaric (2), kaurenoic (3), benzoylgrandifloric (4) and cinnamoylgrandifloric (5) acids in dried leaves of Mikania species stored in dark room under controlled conditions. Excepting 2, the constituents were isolated and purified to be employed as reference compounds. The samples were analyzed at three monthly intervals up to 18 months for M. laevigata and 12 months for M. glomerata. trans-o-Coumaric was not detected in both, whereas 1 occurred only in M. laevigata. The concentrations of the assayed constituents did not vary significantly within the evaluated period (p < 0.05), for both species. In contrast, changes in the chromatographic profiles and spectral purity of peaks from 3, 4 and 5 were detected in samples of both Mikania stored for three months, while the coumarin profile in M. laevigata modified after six months of storage. The evaluation of chromatographic profiles based on spectral purity analyses of selected peaks was shown to be a more robust tool to access chemical stability of Mikania samples than the quantitation of chemical markers' contents.
Asunto(s)
Cinamatos/aislamiento & purificación , Diterpenos de Tipo Kaurano/aislamiento & purificación , Mikania/química , Extractos Vegetales/química , Cromatografía Líquida de Alta Presión , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Factores de TiempoRESUMEN
Coumarin (1) and kaurane-type diterpenes are considered the bioactive constituents of Mikania glomerata and M. laevigata, used in Brazil to treat respiratory affective disorders. The seasonal variation of 1, ortho-coumaric acid (2), benzoylgrandifloric acid (3), cinnamoylgrandifloric acid (4), and kaurenoic acid (5) in leaves of both species, cultivated in full sunlight and under shade levels of 40 and 80%, was quantified by HPLC. Compound 2 was detected solely in M. laevigata in concentrations below the limit of quantification. Coumarin was not found in M. glomerata, whereas its concentration reached 0.94±0.24% (w/w) in M. laevigata farmed in summer under 80% shading. Both Mikania species produced higher amounts of kaurane diterpenes when cultivated in plenty of sunlight. Hence, maximum contents of 1 are reached in M. laevigata cultivated under high shading, but with reduced concentrations of 3-5. Conversely, M. glomerata should be cultivated under full sunlight and harvested in winter for highest concentrations of kaurane-type diterpenes.
Asunto(s)
Cumarinas/análisis , Diterpenos de Tipo Kaurano/análisis , Mikania/química , Hojas de la Planta/química , Estaciones del Año , Luz SolarRESUMEN
This paper reports on the syntheses and spectrometric characterisation of eleven novel ent-kaurane diterpenoids, including a complete set of (1)H, (13)C NMR and crystallographic data for two novel ent-kaurane diepoxides. Moreover, the antineoplastic cytotoxicity for kaurenoic acid and the majority of ent-kaurane derivatives were assessed in vitro against a panel of fourteen cancer cell lines, of which allylic alcohols were shown to be the most active compounds. The good in vitro antimalarial activity and the higher selectivity index values observed for some ent-kaurane epoxides against the chloroquine-resistant W2 clone of Plasmodium falciparum indicate that this class of natural products may provide new hits for the development of antimalarial drugs.
Asunto(s)
Antimaláricos/farmacología , Antineoplásicos/farmacología , Diterpenos de Tipo Kaurano/farmacología , Plasmodium falciparum/efectos de los fármacos , Antimaláricos/síntesis química , Antimaláricos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Diterpenos de Tipo Kaurano/síntesis química , Diterpenos de Tipo Kaurano/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Modelos Moleculares , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Relación Estructura-ActividadRESUMEN
Ethnomedicinal informations point to some Aspidosperma species (Apocynaceae) as antimalarial plants in Brazil and have motivated the evaluation of six species which were collected in the state of Minas Gerais: A. cylindrocarpon Müll. Arg., A. parvifolium A. DC., A. olivaceum Müll. Arg., A. ramiflorum Müll. Arg., A. spruceanum Benth. ex Müll. Arg. and A. tomentosum Mart.. A total of 23 extracts of different plant parts in different solvents were assayed in vitro against chloroquine-resistant (W2) and chloroquine-sensitive (3D7) strains of Plasmodium falciparum. All the extracts were shown to be active with IC50 values in the range of 5.0 ± 0 2.8 µg/mL to 65.0 ± 4.2 µg/mL. TLC profile of the extracts revealed the presence of alkaloids in the six species assayed. These results seem to confirm the popular use of Aspidosperma species to treat human malaria in Brazil and seem point to alkaloids as the putative active compounds of the assayed species.
Asunto(s)
Antimaláricos/farmacología , Aspidosperma/química , Extractos Vegetales/farmacología , Plasmodium falciparum/efectos de los fármacos , Aspidosperma/clasificación , Humanos , Concentración 50 Inhibidora , Pruebas de Sensibilidad ParasitariaRESUMEN
A recent reinvestigation of aerial parts of Wedelia paludosa D.C. is described and reports, for the first time, the isolation of iso-kaurenoic acid from this species.
Asunto(s)
Diterpenos/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Wedelia/química , Diterpenos/química , Diterpenos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
A recent reinvestigation of aerial parts of Wedelia paludosa D.C. is described and reports, for the first time, the isolation of iso-kaurenoic acid from this species.
Uma recente reinvestigação das partes aéreas de Wedelia paludosa D.C. é descrita e relata, pela primeira vez, o isolamento do ácido iso-caurenóico desta espécie.
Asunto(s)
Diterpenos/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Wedelia/química , Diterpenos/química , Diterpenos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
Malaria remains one of the most serious world health problem and the major cause of mortality and morbidity in the endemic regions. Brazil is among the 30 high-burden countries and most of the cases occur in the Legal Amazonian Region. New chemotherapeutical agents are needed for the treatment of malaria. Many plant species are used in traditional medicines of malarious countries and a relatively few number of these have been investigated for evaluation of their antimalarial effect. Still lower is the number of those that have had the active natural compounds isolated and the toxicity determined. This area is, then, of great research interest. discovery project of antimalarial natural products from plants traditionally used to treat malaria must include in vitro and in vivo assays as well as bioguided isolation of active compounds. The final products would be antimalarial chemical entities, potential new drugs or templates for new drugs development, and/or standardized antimalarial extracts which are required for pre-clinical and clinical studies when the aim is the development of effective and safe phythomedicines. This review discusses these two approaches, presents briefly the screening methodologies for evaluation of antimalarial activity and focuses the activity of alkaloids belonging to different structural classes as well as its importance as new antimalarial drugs or leads and chemical markers for phytomedicines.
A malária ainda é um dos mais sérios problemas de saúde pública e a principal causa de mortalidade e morbidade nas regiões endêmicas. O Brasil está entre os 30 países com maior incidência de malária e a maior parte dos casos ocorre na Amazônia Legal. Novos agentes terapêuticos são necessários para o tratamento da malária. Muitas espécies vegetais são utilizadas na medicina tradicional de vários países endêmicos mas é relativamente reduzido o número daquelas que já foram investigadas quanto à sua atividade antimalárica. Menor ainda é o número de espécies das quais foram isoladas substâncias ativas e tiveram sua toxidade determinada. Esta área de pesquisa é, portanto, de alta relevância. Um projeto de descoberta de produtos naturais antimaláricos a partir de plantas de uso tradicional deve incluir ensaios in vitro e in vivo bem como o isolamento biomonitorado de substâncias ativas. Os produtos finais serão substâncias naturais antimaláricas, potenciais fármacos ou protótipos para o desenvolvimento de novos fármacos, e/ou extratos padronizados, com atividade antimalárica, os quais são necessários para estudos pré-clínicos e clínicos quando o objetivo é o desenvolvimento de fitoterápicos (fitomedicamentos) eficazes e seguros. A presente revisão discute estas duas abordagens, apresenta resumidamente as metodologias de bioensaios para avaliação de atividade antimalárica e focaliza a atividade de alcalóides pertencentes a diferentes classes estruturais bem como sua importância como fármacos ou protótipos e como marcadores químicos de fitoterápicos.
Asunto(s)
Animales , Humanos , Alcaloides , Antimaláricos , Plantas Medicinales/química , Alcaloides/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Antimaláricos/química , Antimaláricos/aislamiento & purificación , Antimaláricos/farmacología , Diseño de Fármacos , FitoterapiaRESUMEN
Malaria remains one of the most serious world health problem and the major cause of mortality and morbidity in the endemic regions. Brazil is among the 30 high-burden countries and most of the cases occur in the Legal Amazonian Region. New chemotherapeutical agents are needed for the treatment of malaria. Many plant species are used in traditional medicines of malarious countries and a relatively few number of these have been investigated for evaluation of their antimalarial effect. Still lower is the number of those that have had the active natural compounds isolated and the toxicity determined. This area is, then, of great research interest. discovery project of antimalarial natural products from plants traditionally used to treat malaria must include in vitro and in vivo assays as well as bioguided isolation of active compounds. The final products would be antimalarial chemical entities, potential new drugs or templates for new drugs development, and/or standardized antimalarial extracts which are required for pre-clinical and clinical studies when the aim is the development of effective and safe phythomedicines. This review discusses these two approaches, presents briefly the screening methodologies for evaluation of antimalarial activity and focuses the activity of alkaloids belonging to different structural classes as well as its importance as new antimalarial drugs or leads and chemical markers for phytomedicines.
Asunto(s)
Alcaloides , Antimaláricos , Plantas Medicinales/química , Alcaloides/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Animales , Antimaláricos/química , Antimaláricos/aislamiento & purificación , Antimaláricos/farmacología , Diseño de Fármacos , Humanos , FitoterapiaRESUMEN
Wedelia paludosa D.C. (Asteraceae) is an ornamental species occurring in many regions of Brazil. Aiming to find new cytotoxic compounds, the hydromethanol extract of W. paludosa (HME), as well as the dichloromethane (DF) and water (WF) fractions resulting from its partition, were submitted to the brine shrimp lethality bioassay (BSLB) in order to evaluate their cytotoxicity. Dichloromethane fraction (DF) was shown to be the most cytotoxic fraction (LC50 = 140.6 μg/mL), and its analysis by reversed phase high performance liquid chromatography (RP-HPLC) revealed ent-kaurenoic (1, 6.22 ± 0.23 percent) and grandiflorenic (2, 3.22 ± 0.31 percent) acids as important constituents. HME (LC50 = 980 μg/mL), DF (LC50 = 140.6 μg/mL), 1 (LC50 = 15.9 μg/mL) and 2 (LC50 = 29.8 μg/mL) were found to be cytotoxic, while the water fraction (WF, LC50 >> 1000 μg/mL) was inactive. As conclusion, the cytotoxicity observed for HME and DF is mainly due to the presence of 1 and 2 in their constitution.
Wedelia paludosa D.C. (Asteraceae) é uma planta ornamental facilmente encontrada em várias regiões do Brasil, principalmente nos estados de Santa Catarina, São Paulo, Minas Gerais, Bahia e Pernambuco. Objetivando descobrir novas substâncias citotóxicas a partir desta espécie, o extrato hidrometanólico de W. paludosa (HME) e as frações diclorometânica (FD) e aquosa (FA) resultantes de sua partição em CH2Cl2-H2O foram avaliados utilizando-se o bioensaio em Artemia salina. A fração diclorometânica (FD) apresentou a maior atividade citotóxica (CL50 = 140,6 μg/mL), e sua análise por cromatografia líquida de alta eficiência empregando-se fase reversa (FR-CLAE) revelou os ácidos caurenóico (1, 6,22 ± 0,23 por cento) e grandiflorênico (2, 3,22 ± 0,31 por cento) como constituintes majoritários. As amostras HME (CL50 = 980 μg/mL), FD (CLC50 = 140,6 μg/mL), 1 (CL50 = 15,9 μg/mL) e 2 (CL50 = 29,8 μg/mL) foram citotóxicas contra A. salina, enquanto que a fração aquosa (FA, CL50 >> 1000 μg/mL) mostrou-se inativa. Conclui-se que a citotoxidade observada para HME e FD pode ser atribuída à presença dos ácidos caurenóico (1) e grandiflorênico (2) nestes extratos.
RESUMEN
The effects of Tabebuia avellanedae (TACE), traditionally prescribed in the treatment of cancer, and the naphtoquinone beta-lapachone (beta-lap) on the growth and differentiation of granulocyte and macrophage progenitor cells (CFU-GM) were studied in Ehrlich ascites tumour-bearing mice. Myelosuppression concomitant with increases in spleen CFU-GM and in serum colony-stimulating activity (CSA) were observed in these animals. Treatment with TACE (30-500 mg/kg) and beta-lap (1-5mg/kg) reversed these effects in a dose-dependent manner. The optimal biologically active doses of 120 mg/kg TACE and 1mg/kg beta-lap prolonged life span of tumour-bearing mice, both producing the same rate of extension in the duration of survival. Toxic manifestations were produced by the higher doses of beta-lap in normal and tumour-bearing mice. In spite of similarities between treatments, TACE concentrations used to treat the animals presented no traces of beta-lap, as measured by TLC and HPLC analyses. Our findings suggest that the antitumour effect of TACE and beta-lap, acting synergistically with other factors, such as specific cytokines, may result from enhanced macrophage activation against tumour cells. In addition, it is clear from our results that hematopoietic disorders produced by tumours are an important pathological condition that must be considered in drug development.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Hematopoyesis/efectos de los fármacos , Naftoquinonas/farmacología , Neoplasias Experimentales/sangre , Tabebuia/química , Animales , Células de la Médula Ósea/efectos de los fármacos , Carcinoma de Ehrlich/sangre , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Factores Estimulantes de Colonias/sangre , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Masculino , Ratones , Ratones Endogámicos BALB C , Mielopoyesis/efectos de los fármacos , Corteza de la Planta/química , Extractos Vegetales/farmacología , Bazo/citología , Bazo/metabolismo , Células Madre/efectos de los fármacos , Análisis de SupervivenciaRESUMEN
The potential antihypertensive activity of Brazilian plants was evaluated in vitro by its ability to inhibit the angiotensin-converting enzyme (ACE). Forty-four plants belonging to 30 families were investigated. Plants were selected based on their popular use as antihypertensive and/or diuretics. The following plants presented significant ACE inhibition rates: Calophyllum brasiliense, Combretum fruticosum, Leea rubra, Phoenix roebelinii and Terminalia catappa.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Fitoterapia , Extractos Vegetales/farmacología , Plantas Medicinales , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Brasil , Calophyllum , Combretum , Humanos , Medicina Tradicional , Componentes Aéreos de las Plantas , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Tallos de la Planta , TerminaliaRESUMEN
Ethanol extract from Arrabidaea triplinervia leaves showed in vitro activity (ED100 5.0 mg/ml) against trypomastigotes of Trypanosoma cruzi, the etiologic agent of Chagas; disease. Bioactivity-directed fractionation of this extract led to the isolation of ursolic and oleanolic acids as trypanocidal compounds besides pomolic acid (not tested) and alpinetine (inactive). A series of natural and synthetic derivatives of ursolic and oleanolic acids was simultaneously assayed for structure activity relationships (SAR) studies. Ursolic acid (ED100 0.4 mg/ml) was four times more active than oleanolic acid (ED100 1.6 mg/ml). The presence of free hydroxy and/or carboxy groups is necessary for the trypanocidal activity as could be deduced from the effect of the acetates, methyl ester, and aldehyde derivatives.
Asunto(s)
Bignoniaceae/química , Triterpenos/farmacología , Tripanocidas/farmacología , Animales , Enfermedad de Chagas/sangre , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/prevención & control , Relación Dosis-Respuesta a Droga , Eritrocitos/efectos de los fármacos , Eritrocitos/parasitología , Espectrometría de Masas/métodos , Ratones , Estructura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/aislamiento & purificación , Ácido Oleanólico/farmacología , Pruebas de Sensibilidad Parasitaria/métodos , Fitoterapia/métodos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Hojas de la Planta/química , Relación Estructura-Actividad , Triterpenos/química , Triterpenos/aislamiento & purificación , Tripanocidas/química , Tripanocidas/aislamiento & purificación , Trypanosoma cruzi/efectos de los fármacos , Trypanosoma cruzi/crecimiento & desarrollo , Ácido UrsólicoRESUMEN
A series of new furoterpenyl-1,4-naphtho(anthra)quinones have been prepared via oxidative cyclization of the corresponding 2-hydroxy-3-butenyl-1,4-naphtho(anthra)quinones. Depending on the reaction conditions the 1,2-quinones or the 1,4-quinones were obtained. Several new furo-1,4-anthraquinones were also obtained by condensation of 2,3-dichloroquinones with 1,3-dicarbonyls. The compounds synthesized have been evaluated for their cytotoxicity against neoplastic cell lines, some of them being effective below the micromolar level.
Asunto(s)
Antineoplásicos/farmacología , Quinonas/farmacología , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masa Bombardeada por Átomos VelocesRESUMEN
The compound 2-hydroxy-3-(1'-propen-3-phenyl)-1,4-naphthoquinone (PHNQ6) was evaluated for activity against Toxoplasma gondii, alone or combined with sulfadiazine. Treatment with PHNQ6 combined with sulfadiazine protected at least 70 and 90% of mice infected with RH and EGS strains, respectively. Mice were treated with PHNQ6 (50 mg/kg/day) alone or combined with sulfadiazine (40 mg/L) 30 days after infection with P strain. The number of brain cysts was lower in mice treated with PHNQ6 alone or combined with sulfadiazine compared to that in control mice. Degenerated bradyzoites were observed in animals treated with PHNQ6. Infectivity of bradyzoites treated with PHNQ6 alone or combined with sulfadiazine was inhibited after in vitro incubation.
Asunto(s)
Antiprotozoarios/farmacología , Naftoquinonas/farmacología , Sulfadiazina/farmacología , Toxoplasma/efectos de los fármacos , Toxoplasmosis Animal/tratamiento farmacológico , Animales , Antiprotozoarios/uso terapéutico , Quimioterapia Combinada , Femenino , Ratones , Naftoquinonas/uso terapéutico , Distribución Aleatoria , Sulfadiazina/uso terapéutico , Resultado del TratamientoRESUMEN
Various Diels Alder cycloaddition conditions have been used to optimise the preparation of cytotoxic 6-alkyl-1, 4-naphthoquinones, which were subsequently transformed into 6(7)-alkyl-2-hydroxy-1, 4-naphthoquinones. The compounds thus prepared were evaluated for their cytotoxic activity against several neoplastic cultured cell lines and some of them showed IC50 values below the microM level.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Naftoquinonas/síntesis química , Naftoquinonas/farmacología , Animales , Antineoplásicos/química , División Celular/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Naftoquinonas/química , Ratas , Células Tumorales CultivadasRESUMEN
A systematic investigation on the trypanocidal effect of several natural products isolated from Brazilian plant species has been carried out. In this paper we report on the results obtained from the screening of 26 diterpenes from natural sources or of synthetic/microbial transformations origin (mainly derivatives of kaurenoic acid) against trypomastigote forms of Trypanosoma cruzi, the causative agent of Chagas'disease. In the in vitro assays, kaurenoic acid, kaurenol, acutifloric acid and stemodin showed a complete elimination of parasites from the blood. Therefore, such diterpenoids can be considered as starting materials for molecular modification in the search for lead compounds for clearance of infected blood to be used in transfusions. Blood previously treated with active compounds was submitted to an infectivity test. Samples proceeded from treatment with kaurenol and kaurenoic acid showed to be completly clean from T. cruzi as no infection was observed in mice inoculated with contaminated blood treated by these compounds.