RESUMO
The research about α-methylene-γ-lactams is scarce; however, their synthesis has emerged in recent years mainly because they are isosters of α-methylene-γ-lactones. This last kind of compound is structurally most common in some natural products' nuclei, like sesquiterpene lactones that show biological activity such as anti-inflammatory, anticancer, antibacterial, etc., effects. In this work, seven α-methylene-γ-lactams were evaluated by their inflammation and α-glucosidase inhibition. Thus, compounds 3-methylene-4-phenylpyrrolidin-2-one (1), 3-methylene-4-(p-tolyl)pyrrolidin-2-one (2), 4-(4-chlorophenyl)-3-methylenepyrrolidin-2-one (3), 4-(2-chlorophenyl)-3-methylenepyrrolidin-2-one (4), 5-ethyl-3-methylene-4-phenylpyrrolidin-2-one (5), 5-ethyl-3-methylene-4-(p-tolyl)pyrrolidin-2-one (6) and 4-(4-chlorophenyl)-5-ethyl-3-methylenepyrrolidin-2-one (7) were evaluated via in vitro α-glucosidase assay at 1 mM concentration. From this analysis, 7 exerts the best inhibitory effect on α-glucosidase compared with the vehicle, but it shows a low potency compared with the reference drug at the same dose. On the other side, inflammation edema was induced using TPA (12-O-tetradecanoylphorbol 13-acetate) on mouse ears; compounds 1-7 were tested at 10 µg/ear dose. As a result, 1, 3, and 5 show a better inhibition than indomethacin, at the same doses. This is a preliminary report about the biological activity of these new α-methylene-γ-lactams.
Assuntos
Anti-Inflamatórios , Inibidores de Glicosídeo Hidrolases , Lactamas , alfa-Glucosidases , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Lactamas/química , Lactamas/farmacologia , Animais , alfa-Glucosidases/metabolismo , Simulação de Acoplamento Molecular , Camundongos , Relação Estrutura-Atividade , Simulação por Computador , Edema/tratamento farmacológico , Edema/induzido quimicamente , Estrutura MolecularRESUMO
Serjania triquetra is a medicinal plant widely used in traditional medicine for the treatment of urinary tract diseases, renal affections, and its complications. The population can buy this plant in folk markets as a raw material mixed with several herbal remedies or as a health supplement. On the market, two commercial presentations were found for the vegetal material; one had a bulk appearance and the other was marketed wrapped in cellophane bags (HESt-2, HESt-3). Nevertheless, the plant has not been exhaustively investigated and quality control techniques have not been developed. This research aimed to realize a phytochemical study using an authentic, freshly collected sample as a reference for S. triquetra (HESt-1), using the compounds identified. A method for the determination of preliminary chromatographic fingerprinting was developed. Additionally, the vasorelaxant effect from three samples was evaluated with ex vivo rat models. Thus, three hydroalcoholic extracts (HESt-1, HESt-2, and HESt-3) were prepared by maceration. A total of nine compounds were fully identified from HESt-1 after the extract was subjected to open-column chromatography. Seven metabolites were detected by gas chromatography, while ursolic acid (UA) and allantoin were isolated and identified using UPLC-MS and NMR, respectively. Three extracts were analyzed for their chromatographic fingerprint by UPLC-MS. Biological activity was explored by ex vivo rat aorta ring model to evaluate vasorelaxant activity. All extracts showed a vasorelaxant effect in a concentration-dependent and endothelium-dependent manner. S. triquetra vascular activity may be attributed to UA and allantoin compounds previously described in the literature for this activity.
RESUMO
Hechtia glomerata, a Mexican medicinal plant employed against bacterial infections and as food, is taxonomically related to the genus Tillandsia which has anticancer activity. Organic and aqueous extracts of H. glomerata leaves were prepared and tested for cytotoxic and antibacterial activity. UPLC-QTOF-MS analysis determined the chemical composition of active extracts to find cytotoxic and antibacterial compounds. Hexane extract was cytotoxic against HepG2, Hep3B and MCF7 (IC50: 24-28 µg/mL), whereas CHCl3/MeOH extract against PC3 and MCF7 (IC50: 25 and 32 µg/mL). CHCl3/MeOH extract showed antibacterial activity against Staphylococcus aureus and Enterococcus faecium (MIC: 125 and 62.5 µg/mL). Hexane extract cytotoxic compounds were ß-sitosterol, stigmasterol, phytol and ursolic acid. CHCl3/MeOH extract antibacterial and/or cytotoxic compounds were daucosterol, oleanolic acid, resveratrol, quercetin, kaempferol, apigenin, cyanidin, p-coumaric acid and caffeic acid. This plant could be useful against bacterial infections and cancer. However, in vivo studies are needed to determine its toxicity and therapeutic efficacy.
Assuntos
Extratos Vegetais , Plantas Medicinais , Antibacterianos/farmacologia , México , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Staphylococcus aureusRESUMO
The search for novel biosurfactants (Bs) requires the isolation of microorganisms from different environments. The Gulf of Mexico (GoM) is a geographical area active in the exploration and exploitation of hydrocarbons. Recent metagenomic and microbiologic studies in this area suggested a potential richness for novel Bs microbial producers. In this work, nineteen bacterial consortia from the GoM were isolated at different depths of the water column and marine sediments. Bs production from four bacterial consortia was detected by the CTAB test and their capacity to reduce surface tension (ST), emulsion index (EI24), and hemolytic activity. These bacterial consortia produced Bs in media supplemented with kerosene, diesel, or sucrose. Cultivable bacteria from these consortia were isolated and identified by bacterial polyphasic characterization. In some consortia, Enterobacter cloacae was the predominant specie. E. cloacae BAGM01 presented Bs activity in minimal medium and was selected to improve its Bs production using a Taguchi and Box-Behnken experimental design; this strain was able to grow and presented Bs activity at 35 g L-1 of NaCl. This Bs decreased ST to around 34.5 ± 0.56 mNm-1 and presented an EI24 of 71 ± 1.27%. Other properties of this Bs were thermal stability, stability in alkaline conditions, and stability at high salinity, conferring important and desirable characteristics in multiple industries. The analysis of the genome of E. cloacae BAGM01 showed the presence of rhlAB genes that have been reported in the synthesis of rhamnolipids, and alkAB genes that are related to the degradation of alkanes. The bioactive molecule was identified as a rhamnolipid after HPLC derivatization, 1H NMR, and UPLC-QTOF-MS analysis.
Assuntos
Enterobacter cloacae/genética , Enterobacter cloacae/metabolismo , Glicolipídeos/química , Tensoativos/química , Bactérias/isolamento & purificação , Golfo do México , Consórcios Microbianos , SalinidadeRESUMO
ETHNOPHARMACOLOGICAL IMPORTANCE: CORDIA MORELOSANA: Standley (Boraginaceae) is commonly used in folk medicine for the treatment of diarrhoea, kidney inflammation, diabetes, lung pain, bronchitis, asthma, hoarseness, cough and fever. AIM: Current work was conducted to develop a bio-guided isolation of antidiabetic compounds from ethanolic extract of Cordia morelosana (EECm). MATERIAL AND METHODS: The phytochemical bio-guided study was conducted by successive chromatographic techniques, and isolated compounds were characterized by 1D and 2D-NMR experiments. The in vivo antihyperglycemic and antidiabetic activities of EECm (100 mg/kg), and methyl rosmarinate (MR, 50 mg/kg) were determined on normoglycemic and diabetic murine models. Additionally, the in vitro activity was conducted to determine α-glucosidase inhibitory effect, and PPARs, GLUT4 and FATP expression on 3T3-L1 cells by RT-PCR. Acute and sub-chronic toxicological studies for EECm were conducted on rats, following the OECD guidelines (No. 420 and 407). RESULTS: EECm promotes significant α-glucosidase inhibition (55.6%) at 1 mg/kg respect to the control. Also, EECm (100 mg/kg) showed significant antihyperglycemic effect on oral glucose tolerance test (OGTT), and in non-insulin dependent type 2 diabetes (NIDD) model, had antidiabetic activity (p < 0.001) compared to controls. The bio-guided isolation allowed to obtain four known compounds described as rosmarinic acid (RA), methyl rosmarinate (MR), nicotiflorine and 1-O-methyl-scyllo-inositol. On the other hand, MR showed significant antidiabetic and anthiyperglycemic activities (p < 0.05), and overexpression of PPARγ, PPARα, GLUT-4 and FATP than control. Docking studies were conducted with PPARγ and PPARα, showing interesting binding mode profile on those targets. Finally, EECm displayed a LD50 > 2000 mg/kg and sub-chronic toxicological study reveals no toxic signs in animals tested compared to control. CONCLUSION: EECm showed significant antihyperglycemic and antidiabetic actions being RA and MR the main antidiabetic metabolites.
Assuntos
Cordia , Hipoglicemiantes , Compostos Fitoquímicos , Extratos Vegetais , Células 3T3-L1 , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Proteínas de Ligação a Ácido Graxo/genética , Transportador de Glucose Tipo 4/genética , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/toxicidade , Masculino , Camundongos , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Ratos Sprague-Dawley , Ratos Wistar , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica , alfa-Glucosidases/metabolismoRESUMO
The sterols ß-sitostenone (1), stigmast-4,6,8(14),22-tetraen-3-one (2), ß-sitosterol (3) and stigmasterol (4), the aromatic derivatives antiarol (5) and gentisic acid (6), the phenylpropanes coniferyl alcohol (7), epoxyconiferyl alcohol (8) and ferulic acid (9), the apocarotenoid vomifoliol (10), the flavonoids naringenin (11), 7,4'-dimethoxytaxifolin (7,4'-dimethoxydihydroquercetin, 12), aromadendrin (13), kaempferol (14), taxifolin (dihydroquercetin, 15), prunin (naringenin-7-O-ß-d-glucoside, 16), populnin (kaempferol-7-O-ß-d-glucoside, 17) and senecin (aromadendrin-7-O-ß-d-glucoside, 18) and the lignans kobusin (19) and pinoresinol (20), were isolated from the dried bark of Cochlospermum vitifolium Spreng (Cochlospermaceae), a Mexican medicinal plant used to treat jaundice, liver ailments and hepatitis C. Fourteen of these compounds were isolated for the first time from this plant and from the Cochlospermum genus. Compounds 3â»4, 6â»7, 9â»11, 13â»17 and 20 have previously exhibited diverse beneficial liver activities. The presence of these compounds in C. vitifolium correlates with the use of this Mexican medicinal plant.
Assuntos
Bixaceae/química , Flavonoides/química , Flavonoides/farmacologia , Lignanas/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Esteróis/química , Esteróis/farmacologia , Animais , Flavonoides/uso terapêutico , Humanos , Lignanas/farmacologia , Lignanas/uso terapêutico , Casca de Planta/química , Extratos Vegetais/uso terapêutico , Esteróis/uso terapêuticoRESUMO
A group of sixteen iridoids isolated from plants used as anti-inflammatory remedies in Mexican folk medicine were evaluated for their potential to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. From these assays, loganic acid (10) was identified as the most promising compound with both COX-1 (36.0 ± 0.6%) and COX-2 (80.8 ± 4.0%) inhibition at 10 µM. Compound 10 shows a better inhibition against the COX-2 enzyme. Other iridoids tested in the present study showed weak or no inhibition against these enzymes. Furthermore, herein are presented key interactions of iridoid 10 with COX-1 and COX-2 enzymes through molecular docking studies. These studies suggest that 10 exhibits anti-inflammatory activity due to COX inhibition.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Iridoides/farmacologia , Orobanchaceae/química , Penstemon/química , Vitex/química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Iridoides/química , Iridoides/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Polypyrrole (PPy) and polypyrrole/polyethylene glycol (PPy/PEG) implants synthesized by chemical, electro-chemical, and plasma polymerization methods were implanted into the injured spinal cord of rats to determine their effect on motor function recovery. Before implantation, the materials were characterized by infrared (IR) spectroscopy. An experimental model of traumatic spinal cord injury (TSCI) by complete transection at thoracic level 9, in rats was used. The polymer implants were inserted immediately after transection. Motor function recovery was evaluated once a week during 5 weeks using the Basso, Beattie and Bresnahan (BBB) motor scale. Histological evaluation was done at the end of the recovery evaluation period using hematoxylin/eosin stain. Results showed that animals implanted with polymers synthesized by plasma had a better integration into the nerve tissue, less inflammatory response and a better functional recovery than animals implanted with polymers synthesized by chemical or electrochemical methods.
En el presente trabajo se comparó el efecto de implantes poliméricos derivados del pirrol (polipirrol o PPy) y del copolímero polipirrol/polietilenglicol (PPy/PEG), obtenidos por diferentes métodos de síntesis: químico, electroquímico y polimerización por plasma con el propósito de determinar si el método de síntesis puede influir sobre el efecto que producen al ser implantados después de una lesión traumática de la médula espinal de ratas. Antes de realizar el implante, las características químicas y estructurales de los polímeros fueron analizadas por espectroscopia de infrarrojo (IR). Se utilizó un modelo experimental de lesión traumática de médula espinal (LTME) por sección completa en ratas. La LTME se realizó a nivel torácico 9 y el polímero fue implantado de inmediato en la zona de lesión. La recuperación de la función motora se evaluó mediante la escala Basso, Beattie y Bresnahan (BBB) una vez por semana durante 5 semanas. La evaluación histológica se realizó al término del seguimiento con la tinción de hematoxilina/eosina. Los resultados muestran que los animales implantados con polímeros sintetizados por plasma se integraron mejor al tejido nervioso, redujeron la respuesta inflamatoria y favorecieron una mayor recuperación funcional en comparación con los animales implantados con materiales sintetizados por métodos químicos o electroquímicos.
RESUMO
Polymers synthesized by plasma derived from pyrrole have been recently implanted in rats with spinal cord injuries (SCI) using a complete section model; the polymers contribute to the functional recovery after the injury. In this work, the SCI in rats was studied using noninvasive techniques such as magnetic resonance imaging (MRI). Also computerized axial tomography taken chronologically with and without polymeric implants. 3D reconstructions were used to follow the structural arrangement, the location of the implant and the formation of cysts. MRI shows a clear differentiation between white and gray matter, the implanted material and cysts due to secondary damage after the injury.
Polímeros sintetizados por plasma derivados del pirrol, han sido implantados en ratas con lesión de médula espinal (LME) usando un modelo de lesión por sección completa; los polímeros contribuyen a la recuperación funcional después de la lesión. En este trabajo, la LME se estudió usando técnicas no invasivas como imágenes por resonancia magnética (IRM) y tomografía axial computarizada tomada cronológicamente en sujetos con y sin implante polimérico. Se usaron reconstrucciones 3D para seguir el arreglo estructural, la localización del implante y la formación de quistes. Las IRM muestran una clara diferenciación entre materia gris, materia blanca, material implantado y quistes formados debido a los mecanismos de daño secundario después de la lesión.
RESUMO
Krameria pauciflora is a species belonging to the Krameriaceae family. It has been used to treat inflammatory disorders in folkloric Mexican medicine; however, chemistry and pharmacological studies have not been carried out on this species. In this work, from the dichloromethane root extract of K. pauciflora, five cycloartane-type triterpenoids were isolated: cyclomargenyl-3-O-ß-caffeoyl ester (1), cyclomargenyl-3-O-ß-feruloyl ester (2), cyclomargenyl-3-O-ß-coumaroyl ester (3), cyclomargenol (4, polysthicol), and cyclomargenone (5). Additionally, the lignane 6'-methoxyrataniaphenol was isolated. To the best of our knowledge, compounds 1-3 are new natural products, whereas compounds 4 and 5 are isolated for the first time in the Krameria genus and the Krameriaceae family. The structures of all of these compounds were established by 1D and 2D NMR spectroscopy including ¹H, ¹³C, DEPT, COSY, HSQC, and HMBC experiments, as well as by EI mass spectrometry. There is an incomplete previous report about the spectroscopic data of compounds 4 and 5. However, in this work, a complete and unambiguous assignation has been realized. Due to the traditional use of this plant and other species from this genus, such as K. lappacea, cycloartanes isolated herein were evaluated by their inhibition of phospholipase A2, cyclooxygenase-1, and cyclooxygenase-2 enzymes. Cyclomargenyl-3-O-ß-caffeoyl ester (1) showed inhibition of phospholipase A2, cyclooxygenase-1, and cyclooxygenase-2 target enzymes for nonsteroidal anti-inflammatory drugs. Both cyclooxygenases were inhibited by cyclomargenol (4); however, cyclomargenyl-3-O-ß-feruloyl ester (2) showed inhibition only on cyclooxygenase-1.
Assuntos
Ácidos Cafeicos/isolamento & purificação , Ácidos Cafeicos/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Krameriaceae/química , Inibidores de Fosfolipase A2 , Extratos Vegetais/farmacologia , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Ácidos Cafeicos/química , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase/química , Medicina Tradicional , México , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Triterpenos/químicaRESUMO
The plant Krameria pauciflora MOC et. Sessé ex DC. is used as an anti-inflammatory and antidiabetic in traditional medicine. The aim of this study was to evaluate the in vivo anti-inflammatory and antidiabetic effects of a methanol extract from the roots of K. pauciflora. Dichloromethane and ethyl acetate extracts obtained by partitioning the methanol extract were also evaluated. Complete methanol and dichloromethane extracts showed anti-inflammatory effects at 3 mg/kg. An anti-inflammatory effect similar to indomethacin (10 mg/kg) was observed when the methanol and dichloromethane extracts, which contain a cycloartane-type triterpene and an sterol, were administered orally at several doses (3, 10, 30 and 100 mg/kg), whereas no anti-inflammatory effect was observed at any dose for the ethyl acetate extract, which contains catechin-type flavonoids. The antidiabetic effect of each extract was also determined. An antihyperglycaemic effect was observed in diabetic rats, but no effect in normoglycaemic animals was observed when the methanol extract was administrated at 30 mg/kg. All of the extracts exhibited radical scavenger activity. Additionally, constituents from all of the extracts were identified by NMR. This article supports the use of K. pauciflora as an anti-inflammatory because it exhibits a similar effect to indomethacin. However, its antidiabetic effect is not completely clear, although it could be useful for preventing diabetic complications.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Sequestradores de Radicais Livres/isolamento & purificação , Hipoglicemiantes/isolamento & purificação , Krameriaceae/química , Metanol/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Área Sob a Curva , Benzotiazóis/química , Compostos de Bifenilo/química , Glicemia , Carragenina , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Pé/patologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Radicais Livres/química , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Masculino , Picratos/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Ácidos Sulfônicos/químicaRESUMO
Heliopsis longipes is used as analgesic in Mexican traditional medicine. The present study assesses the possible antinociceptive effect of Heliopsis longipes and describes the pharmacological mechanism of action of the antinociceptive effect of affinin, identified as the one active principle in Heliopsis longipes acetone extract. Intraperitoneal administration of H. longipes extract and affinin produced a dose-dependent antinociceptive effect when assessed in mice submitted to acetic acid and capsaicin tests. Affinin-induced antinociception (30 mg/kg, I. P.) was blocked by naltrexone (1 mg/kg, S. C.), P-chlorophenylalanine (80 mg/kg, I. P.) and flumazenil (5 mg/kg, S. C.) suggesting that its pharmacological effect could be due to the activation of opiodergic, serotoninergic and GABAergic systems. In addition, the antinociceptive effect of affinin was attenuated by pretreatment with 1 H-[1,2,4]oxadiazolo[1,2- A]quinoxalin-1-one (1 mg/kg, S. C.) and glibenclamide (10 mg/kg, S. C.) suggesting that the nitric oxide-K (+) channels pathway could be involved in its mechanism of action. These results suggest that affinin itself or its derivatives may have potential antinociceptive effects.
Assuntos
Analgésicos/isolamento & purificação , Asteraceae/química , Extratos Vegetais/química , Alcamidas Poli-Insaturadas/isolamento & purificação , Ácido Acético , Analgésicos/farmacologia , Animais , Capsaicina , Avaliação Pré-Clínica de Medicamentos , Masculino , México , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Alcamidas Poli-Insaturadas/farmacologiaRESUMO
Heliopsis longipes (Compositae) is a Mexican plant used as analgesic in pain toothache. A solution of 10mug/ml of dichloromethane extract from this plant showed analgesic activity determined by means of GABA release in mice brain slices. Through a bioassay-directed separation, fractions G-1, G-2, G-4 and G-6 at the same concentration were active. Affinin was the unique and common active compound, and evoke the GABA release 0.5min after administration at 1x10(-4)M concentration. Inactive compound were undeca-2E-en-8,10-dyinoic acid isobutylamide, hinokinin, 2'-hydroxyhinokinin, 3beta-sn-glyceroyl-(1''-palmitoxy)urs-12-ene, 13(18)-ursen-3beta-ol, 13(18)-ursen-3beta-acetate, beta-sitosterol and stigmasterol. The analgesic activity of Heliopsis longipes could be associated to affinin.
Assuntos
Alcenos/farmacologia , Amidas/farmacologia , Analgésicos/farmacologia , Asteraceae/química , Dor/tratamento farmacológico , Extratos Vegetais/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , 4-Butirolactona/análogos & derivados , 4-Butirolactona/isolamento & purificação , Alcenos/isolamento & purificação , Amidas/isolamento & purificação , Analgésicos/isolamento & purificação , Animais , Benzodioxóis , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dioxóis/isolamento & purificação , Feminino , Técnicas In Vitro , Lignanas/isolamento & purificação , Medicina Tradicional , Cloreto de Metileno , México , Camundongos , Plantas Medicinais , Alcamidas Poli-Insaturadas/isolamento & purificação , Ácido gama-Aminobutírico/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismoRESUMO
Four new phorbol derivatives, 12-O-[(2R)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetate (1), 12-O-[(2S)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetate (2), 12-O-[3-methyl-2-butenoyl]-4-deoxyphorbol 13-acetate (3), and 12-O-[(2R)-N,N-dimethyl-3-methylbutanoyl]phorbol 13-acetate (4), along with six known compounds, were isolated from the aerial parts of Croton ciliatoglandulifer. An anti-inflammatory activity of a hexane extract of this plant was demonstrated against ear edema in mice produced by 12-O-tetradecanoylphorbol 13-acetate, and compounds 1, 4, and 3beta-O-acetyloleanolic acid (5) were active when evaluated against cyclooxygenases-1 and -2.
Assuntos
Anti-Inflamatórios não Esteroides/isolamento & purificação , Croton/química , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Nitrogênio/química , Ésteres de Forbol/isolamento & purificação , Plantas Medicinais/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 1/efeitos dos fármacos , Ciclo-Oxigenase 2/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Modelos Animais de Doenças , Orelha , Edema/induzido quimicamente , Edema/tratamento farmacológico , México , Camundongos , Ésteres de Forbol/química , Ésteres de Forbol/farmacologia , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
The structure elucidation and 1H and 13C assignments of the new triterpenes 3beta-palmitoxy-7beta-hydroxyolean-12-ene (1) and its hydrolysis product 3beta,7beta-dihydroxyolean-12-ene (2) and 3beta-sn-glyceroyl-(1''-palmitoxy)urs-12-ene (3), isolated from the aerial parts of Cladocolea grahami (Loranthaceae), are reported.
Assuntos
Plantas Medicinais/química , Triterpenos/química , Hidrólise , Espectroscopia de Ressonância Magnética/métodos , Estrutura Molecular , Triterpenos/isolamento & purificaçãoRESUMO
Three new sesquiterpenes, 5alpha,7alpha,10betaH-3-patchoulen-2-one (1), 5alpha,7alpha10betaH-4(14)-patchoulen-2alpha-ol (2), and 9alpha,10beta-dihydroxy-2beta,4beta-peroxy-1alpha,5beta,7alphaH-guaiane (3), were isolated from the aerial parts of Croton arboreous along with 14 known compounds. The structures of these compounds were determined on the bases of their spectroscopic data (IR, UV, OR, 1D and 2D NMR, and MS). The anti-inflammatory activity against ear edema in mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) was evaluated for all the pure compounds and showed that compounds 4-7 are active.
Assuntos
Anti-Inflamatórios não Esteroides/isolamento & purificação , Croton/química , Plantas Medicinais/química , Sesquiterpenos/isolamento & purificação , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Orelha , Edema/induzido quimicamente , México , Camundongos , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Guaiano , Estereoisomerismo , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Through a bioactivity-guided fractionation from the acetone extract of the leaves from Esenbeckia yaaxhokob geranyl N-dimethylallylanthranilate ( 1), the first natural N- and O-prenylated anthranilate, was isolated in addition of the known natural products caryophyllene beta-oxide, caryolane-5beta,9beta-diol, spathulenol ( 2), friedeline, friedelanol, decaprenol, flindersiamine ( 3) and beta-sitosterol. The antimicrobial activities of the extract, fractions and pure compounds were evaluated against two Gram (+) and four Gram (-) bacteria. Compounds 1 and 2 exhibited moderated antimicrobial activity against Staphyloccocus aureus, while 3 was active against S. aureus and Streptococcus faecalis.
Assuntos
Anti-Infecciosos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Plantas Medicinais , ortoaminobenzoatos/farmacologia , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Humanos , Medicina Tradicional , México , Testes de Sensibilidade Microbiana , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Folhas de Planta , ortoaminobenzoatos/administração & dosagem , ortoaminobenzoatos/uso terapêuticoRESUMO
Carcinoma of the uterine cervix is the most frequent malignancy in women in developing countries. Based on the possible synergistic effect of the combination of interferon and radiotherapy, a clinical trial was conducted in patients with advanced cervical cancer. The objective was to evaluate the efficacy and security of such a therapeutic approach. This prospective phase II trial was done at the Instituto Nacional de Cancerología in Mexico City. The study included 17 consecutive patients with previously untreated squamous cell cervical cancer, clinical stages III and IV, and tumor mean size of 9.7 cm. The patients received radiotherapy and interferon alpha-2b at a dose of 5 x 106 IU/m2 3 times a week for 6 weeks. Eleven (64%) complete responses were obtained among these patients. Long-term survival was observed in 4 patients (24%) who achieved complete response and are alive after 10 years of follow-up. Immediate toxicity was mild. Late toxicity included the development of proctitis in 13 patients, colostomy was performed in 3 (23%) of them. Our results indicate that the combination of radiotherapy and this cytokine is an active therapy for squamous cell carcinoma of the uterine cervix.
RESUMO
The objective of this study is to provide additional information on the effect of copper ion (Cu2+) in preventing pregnancy. Human spermatozoa, selected by the swim-up method, were incubated for 0, 5 or 24 h in the presence of 10 ng, 1 microgram, 10 micrograms or 100 micrograms of Cu2+ mL-1 in BWW culture medium, and then evaluated in terms of their motility, viability, acrosome reaction (AR) and the capacity to penetrate zona-free hamster eggs. AR and penetration in zona-free hamster eggs were assessed at 5 h of incubation. Motility, viability and AR in sperm incubated for 5 h were significantly affected by Cu2+ at a concentration of 100 micrograms mL-1, but not at the lower concentrations. Incubation for 24 h did not affect motility and viability of sperm incubated in the presence of concentrations of Cu2+ ranging from 10 ng mL-1 to 10 micrograms mL-1, but a concentration of 100 micrograms mL-1 caused a significant decrease in both parameters. In contrast, the penetration rate of zona-free hamster oocytes significantly decreased compared with that of controls, when only sperm were incubated in the presence of concentrations of Cu2+ ranging from 10 ng mL-1 to 10 micrograms mL-1, and no penetration was observed in the presence of 100 micrograms mL-1 of Cu2+ . When only oocytes were exposed to Cu2+, the penetration rate dropped to 50% of that of the controls. Finally, when both gametes were exposed to Cu2+ before co-incubation, the penetration rate fell to zero for every concentration tested. Results showed that copper, at concentrations similar to those released from intrauterine devices (IUD), affects the fertilizing capacity of human gametes in vitro and interferes with the sperm-oocyte interaction leading to fertilization. These effects suggest that the principle action of Cu2+ released from Cu-IUD is to act as a preconception contraceptive agent when delivered in endometrial and oviducal fluids.
Assuntos
Cobre/farmacologia , Fertilização/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Acrossomo/efeitos dos fármacos , Acrossomo/fisiologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Anticoncepcionais/química , Cricetinae , Relação Dose-Resposta a Droga , Feminino , Fertilização/fisiologia , Humanos , Masculino , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Gravidez , Capacitação Espermática/efeitos dos fármacos , Capacitação Espermática/fisiologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Motilidade dos Espermatozoides/fisiologia , Interações Espermatozoide-Óvulo/efeitos dos fármacos , Interações Espermatozoide-Óvulo/fisiologia , Espermatozoides/fisiologia , Fatores de TempoRESUMO
Oocyte donation programs offer an alternative treatment for infertile women with ovarian failure or abnormal ovarian function. Seventeen cycles of in vitro fertilization and embryo transfer with donated oocytes were performed in 13 women, with a mean age of 34.8 years. The hormonal replacement therapy consisted of a fixed dose of oral estradiol valerate, 6 mg daily, and intramuscular progesterone in oil, 100 mg daily. Estrogen and progesterone were continued for 10 more weeks after embryo transfer if pregnancy was established. After 13 embryo transfers, 8 pregnancies were obtained, for a pregnancy rate per transfer of 61.5%. Today seven pregnancies are progressing normally, including one set of twins. This results suggest that an oocyte donation program using a fixed and simple hormonal replacement therapy is an adequate treatment for these infertile couples.