RESUMO
Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is one of the most important neglected diseases in Latin America. The limited use of the current nitro-derivative-based chemotherapy highlights the need for alternative drugs and the identification of their molecular targets. In this study, we investigated the trypanocidal effect of the sesquiterpene lactone dehydroleucodine (DhL) and its derivatives, focusing on the antioxidative defense of the parasites. DhL and two derivatives, at lesser extent, displayed antiproliferative effect on the parasites. This effect was blocked by the reducing agent glutathione (GSH). Treated parasites exhibited increased intracellular ROS concentration and trypanothione synthetase activity, accompanied by mitochondrial swelling. Although molecular dynamics studies predicted that GSH would not interact with DhL, 1H-NMR analysis confirmed that GSH could protect parasites by interacting with the lactone. When parasites overexpressing mitochondrial tryparedoxin peroxidase were incubated with DhL, its effect was attenuated. Overexpression of cytosolic tryparedoxin peroxidase also provided some protection against DhL. These findings suggest that DhL induces oxidative imbalance in T. cruzi, offering new insights into potential drug targets against this parasite.
Assuntos
Lactonas , Espécies Reativas de Oxigênio , Sesquiterpenos , Trypanosoma cruzi , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/metabolismo , Sesquiterpenos/farmacologia , Lactonas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Tripanossomicidas/farmacologia , Glutationa/metabolismo , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Proteínas de Protozoários/metabolismo , Animais , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Amida SintasesRESUMO
Haemonchus contortus, a blood-feeding parasite in grazing sheep, causes economic losses. Drug resistance necessitates exploring plant-based anthelmintics like Artemisia cina (Asteraceae). The plant, particularly its ethyl acetate extract, shows anthelmintic activity against H. contortus. However, there is limited information on pharmacodynamic interactions in ethyl acetate compounds. The study aims to identify pharmacodynamic interactions in the ethyl acetate extract of A. cina with anthelmintic effects on H. contortus eggs and L3 larvae using binary mixtures. Bioactive compounds were isolated via chromatography and identified using spectroscopic techniques. Pharmacodynamic interactions were assessed through binary mixtures with a main compound. Four bioactive compounds were identified: 1-nonacosanol, hentriacontane, peruvin, and cinic acid. Binary mixtures, with peruvin as the main compound, were performed. Peruvin/1-nonacosanol-hentriacontane and peruvin/cinic acid mixtures demonstrated 1.42-fold and 4.87-fold increased lethal effects in H. contortus L3 infective larvae, respectively, at a 0.50LC25/0.50LC25 concentration. In this work, we determined the synergism between bioactive compounds isolated from the ethyl acetate extract of A. cina and identified unreported compounds for the specie.
RESUMO
Sesquiterpene lactones (SL) represent a class of secondary metabolites found in the Asteraceae family, notable for their unique structures. The SL α-santonin (1) and its derivatives are worthy of mention due to their diverse biological properties. Additionally, 4H-chromenes and 4H-chromones are appealing frameworks holding the capability to be used as structural motifs for new drugs. Furthermore, unambiguous structural elucidation is crucial for developing novel compounds for diverse applications. In this context, it is common to find in the literature molecules erroneously assigned. Therefore, the use of quantum mechanical calculations to simulate NMR chemical shifts has emerged as a valuable strategy. In this work, we conceived the synthesis of two halogenated 4H-chromenediones derived from photosantonic acid (2), a photoproduct arising from irradiation of α-santonin (1) in the ultraviolet region. The structure of the chlorinated and brominated products was determined by NMR analysis, with the aid of quantum mechanical calculations at the B3LYP/6-311 + G(2d,p)//M062x/6-31 + G(d,p) level of theory. All analyses were in agreement and led to the assignment of the brominated 4H-chromene-2,7-dione as (3S,3aS,5aR,9bS)-5a-(2-bromopropan-2-yl)-3-methyl-3,3a,5,5a,8,9b-hexahydro-4H-furo[2,3-f]chromene-2,7-dione (11b) and of the chlorinated 4H-chromene-2,7-dione as (3S,3aS,5aR,9bS)-5a-(2-chloropropan-2-yl)-3-methyl-3,3a,5,5a,8,9b-hexahydro-4H-furo[2,3-f]chromene-2,7-dione (12b). The diastereoselectivities of the reactions were explained based on products and intermediates formation energy calculated using B3LYP/6-31 + G(d,p) as the level of theory. Structures 11b and 12b were identified as the thermodynamic and kinetic products of the reaction among all candidates. Consequently, the strategy utilized in this study is robust and successfully illustrates the use of quantum mechanical calculations in the structural elucidation of new compounds with potential applications as novel drugs or products.
RESUMO
Chagas disease is an infection caused by the protozoan Trypanosoma cruzi, affecting 6-8 million people worldwide. Only two drugs are available for its treatment, having a limited efficacy and adverse side-effects. Estafietin is a sesquiterpene lactone isolated from Stevia alpina with in vitro activity against T. cruzi and low cytotoxicity against mammalian cells. The aim of this work was to predict the toxicologic profile of estafietin by in silico methods and assess its in vivo activity on a murine model of Chagas disease. Estafietin showed low toxicity according to pkCSM web tool and passed the PAINS filter from PAINS-remover web server. The treatment of infected mice with 1 mg/Kg/day of estafietin for five consecutive days administrated by intraperitoneal route significatively decreased parasitemia levels and reduced inflammatory infiltrates and myocyte damage on muscle tissue. These results suggest that estafietin had effect both on acute and chronic stages of the infection.
Assuntos
Doença de Chagas , Stevia , Tripanossomicidas , Trypanosoma cruzi , Humanos , Camundongos , Animais , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêutico , Doença de Chagas/tratamento farmacológico , Sesquiterpenos de Guaiano/farmacologia , Parasitemia/tratamento farmacológico , Lactonas/farmacologia , Lactonas/uso terapêutico , MamíferosRESUMO
Sesquiterpene lactones are found in plants of Asteraceae family, and endoperoxides are known for their antimalarial activity. Structural elucidation is a relevant aspect; however, it is not uncommon to find incorrect or incomplete structural assignments in the literature. Calculations based in quantum mechanics are frequently used to compute 1 H and 13 C NMR chemical shifts, and after comparing with the experimental data, the correct structure is established from diverse candidates. Targeting the synthesis of bioactive compounds, we envisaged the synthesis of a novel endoperoxide from the natural sesquiterpene lactone α-santonin (2). Photochemical transformation of α-santonin (2) to mazdasantonin (4) followed by photooxidation catalyzed by rose bengal afforded the novel endoperoxide 5. This new endoperoxide contains five stereogenic centers and is analogous to the antimalarial agent artemisinin (1). The relative configuration of the stereogenic centers of the endoperoxide were established by nuclear magnetic resonance (NMR) analyses and confirmed by theoretical calculations. All approaches were in complete agreement, and the structure of mazdasantonin endoperoxide was established as (3S,3aS,5aS,8R,9bS)-3,6,6-trimethyl-3,3a,4,5,8,9b-hexahydro-2H-5a,8-epidioxynaphtho[1,2-b]furan-2,7(6H)-dione.
RESUMO
Sesquiterpene lactones are of pharmaceutical interest due their cytotoxic and antitumor properties, which are commonly found within plants of several genera from the Asteraceae family such as the Decachaeta genus. From Decachaeta incompta four heliangolide, namely incomptines A-D have been isolated. In this study, cytotoxic properties of incomptine A (IA) were evaluated on four lymphoma cancer cell lines: U-937, Farage, SU-DHL-2, and REC-1. The type of cell death induced by IA and its effects on U-937 cells were analyzed based on its capability to induce apoptosis and produce reactive oxygen species (ROS) through flow cytometry with 4',6-diamidino-2-phenylindole staining, dual annexin V/DAPI staining, and dichlorofluorescein 2',7'-diacetate, respectively. A differential protein expression analysis study was carried out by isobaric tags for relative and absolute quantitation (iTRAQ) through UPLC-MS/MS. Results reveal that IA exhibited cytotoxic activity against the cell line U-937 (CC50 of 0.12 ± 0.02 µM) and the incubation of these cells in presence of IA significantly increased apoptotic population and intracellular ROS levels. In the proteomic approach 1548 proteins were differentially expressed, out of which 587 exhibited a fold-change ≥ 1.5 and 961 a fold-change ≤ 0.67. Most of these differentially regulated proteins are involved in apoptosis, oxidative stress, glycolytic metabolism, or cytoskeleton structuration.
Assuntos
Apoptose/efeitos dos fármacos , Linfoma não Hodgkin/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/farmacologia , Asteraceae/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida/métodos , Humanos , Linfoma não Hodgkin/patologia , Mapas de Interação de Proteínas/efeitos dos fármacos , Espectrometria de Massas em Tandem/métodos , Células U937RESUMO
Gliomas are responsible for more than 60% of all primary brain tumors. Glioblastoma multiforme (GBM), a grade IV tumor (WHO), is one of the most frequent and malignant gliomas. Despite two decades of advances in the discovery of new markers for GBM, the chemotherapy of choice falls to temozolomide after surgery and radiotherapy, which are not enough to increase the survival of patients to more than 15 months. It is urgent to discover new anti-glioma compounds. Many compounds derived from natural products have been used in the development of anti-tumor drugs. In this work, we have screened six low molecular weight sesquiterpene lactones, isolated from Eremanthus spp., and studied their function as anti-proliferative agents against GBM strains. We demonstrated that two of them, goyazensolide and lychnofolide, were effective in reducing cell viability, preventing the formation of anchorage-dependent colony and were able to pass through a mimetic blood-brain barrier making them candidates for glioma therapy, being more potent than temozolomide, according to in vitro assays for the cell lines tested. Proteomic analysis revealed a number of altered proteins involved in glycolytic metabolism and cellular catabolism.
Assuntos
Lactonas/farmacologia , Vernonia/metabolismo , Antineoplásicos/farmacologia , Asteraceae , Barreira Hematoencefálica/metabolismo , Neoplasias Encefálicas/metabolismo , Brasil , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Furanos/farmacologia , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioma/metabolismo , Humanos , Lactonas/metabolismo , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Sesterterpenos/farmacologia , Vernonia/fisiologiaRESUMO
Peptic ulcer disease, the most common gastrointestinal disorder, is currently treated with several types of drugs, but all have severe side effects. The aim of the present study was to evaluate the gastroprotective activity of juanislamin, isolated from Calea urticifolia, in a rat model of ethanol-induced gastric lesions. Thirty minutes after orally administering a given dose of juanislamin (from 1 to 30 mg/kg) or carbenoxolone (the reference drug, at 1-100 mg/kg) to rats, 1 mL of ethanol was applied, and the animals were sacrificed 2 h later. The stomachs were removed and opened to measure the total area of lesions in each. To examine the possible participation of prostaglandins, nitric oxide and/or sulfhydryl groups in the mechanism of action of juanislamin, the rats received indomethacin, NG-Nitro-l-arginine methyl ester hydrochloride (l-NAME) or N-ethylmaleimide pretreatment, respectively, before being given juanislamin and undergoing the rest of the methodology. Juanislamin inhibited gastric lesions produced by ethanol in a non-dose-dependent manner, showing the maximum gastroprotective effect (100%) at 10 mg/kg. The activity of juanislamin was not modified by pretreatment with indomethacin, l-NAME or N-ethylmaleimide. In conclusion, juanislamin protected the gastric mucosa from ethanol-induced damage, and its mechanism of action apparently does not involve prostaglandins, nitric oxide or sulfhydryl groups.
Assuntos
Antiulcerosos/administração & dosagem , Asteraceae/química , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Óxido Nítrico/farmacologia , Prostaglandinas/farmacologia , Úlcera Gástrica/prevenção & controle , Compostos de Sulfidrila/farmacologia , Animais , Carbenoxolona/administração & dosagem , Etilmaleimida/farmacologia , Mucosa Gástrica/patologia , Indometacina/farmacologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológicoRESUMO
We investigated the immunomodulatory, antiparasitic and cardioprotective effects of a sesquiterpene lactone (SL) administered alone or combined with benznidazole (Bz), in a murine model of Chagas' disease by in vitro and in vivo assays. Antiparasitic and cytotoxic potential of tagitinin C (SL) and Bz were tested in vitro against T. cruzi epimastigotes and cardiomyocytes. Swiss mice challenged with T. cruzi were also treated for 20â¯days with tagitinin C (10â¯mg/kg) alone and combined with Bz (100â¯mg/kg). Tagitinin C exhibited a higher antiparasitic (IC50: 1.15⯵M) and cytotoxic (CC50 at 6.54⯵M) potential than Bz (IC50: 35.81⯵M and CC50: 713.5⯵M, respectively). When combined, these drugs presented an addictive interaction, determining complete suppression of parasitemia and parasitological cure in all infected mice (100%) compared to those receiving Bz alone (70%). Anti-T. cruzi immunoglobulin G, and pro-inflammatory cytokines IFN-γ and TNF-α levels were reduced in animals treated with tagitinin C combined with Bz, while IL-10 production was unaffected. Heart inflammation was undetectable in 90% of the animals receiving this combination, while only 50% of the animals receiving Bz alone showed no evidence of myocarditis. Together, our findings indicated that the combination of tagitinin C and Bz exerts potent antiparasitic, immunomodulatory and cardioprotective effects. Due to the remarkable suppression of parasitemia and high parasitological cure, this combination was superior to Bz monotherapy, indicating a high potential for the treatment of Chagas's disease.
Assuntos
Antiparasitários/farmacologia , Cardiotônicos/farmacocinética , Fatores Imunológicos/farmacologia , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Cardiotônicos/farmacologia , Linhagem Celular , Doença de Chagas/tratamento farmacológico , Doença de Chagas/metabolismo , Doença de Chagas/parasitologia , Citocinas/metabolismo , Feminino , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/parasitologia , Camundongos , Miocardite/metabolismo , Miocardite/parasitologia , Nitroimidazóis/farmacologia , Parasitemia/tratamento farmacológico , Parasitemia/metabolismo , Parasitemia/parasitologia , Ratos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Sesquiterpene lactones are organic compounds derived mainly from plants that exhibit anti-inflammatory and antitumor activities being one of the key mechanism of action of NF-kB pathway and synthesis of cytokines such as IL-1 and TNF- α. AIM OF THE STUDY: The overall objective of the present study was to evaluate the anti-inflammatory action of a sesquiterpene lactone diacethylpiptocarphol (DPC) from Vernonia scorpioides (Lam.) Pers. and parthenolide (PTH) in Balb-c mice with DSS-induced colitis. MATERIALS AND METHODS: The anti-inflammatory effects of Intraperitonial administration of DPC (5â¯mg/kg/day) were evaluated in Balb/c mice with DSS-induced colitis, and further the body weight measurement, TNF-α and TGF-ß level was determined. RESULTS: After intraperitoneal treatment for one week, DSS-induced colitis was significantly reduced in mice treated with either of both sesquiterpenes lactones, as witnessed by reduced cellular infiltration, tissue damage, TNF-α production, and enhanced production of TGF-ß. CONCLUSIONS: Sesquiterpene lactone DPC, isolated from Vernonia scorpioides showed anti-inflammatory activity, in this experimental model of colitis the sesquiterpene lactones DPC and PTH exhibit equal anti-inflammatory activity.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/tratamento farmacológico , Lactonas/uso terapêutico , Sesquiterpenos/uso terapêutico , Vernonia , Animais , Colite/sangue , Colite/induzido quimicamente , Colite/patologia , Colo/efeitos dos fármacos , Colo/patologia , Sulfato de Dextrana , Flores , Injeções Intraperitoneais , Masculino , Camundongos Endogâmicos BALB C , Folhas de Planta , Fator de Crescimento Transformador beta/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
Sesquiterpene lactones (SL) are commonly found in Asteraceae and present a promising anti-inflammatory activity. Previously described in Lepidaploa genus, glaucolide B has never been investigated for its anti-inflammatory potential. This study aimed to establish an efficient process for the extraction of glaucolide B (1) from Lepidaploa chamissonis leaves and to develop a simple and fast method for its purification by using centrifugal partition chromatography (CPC), as well as to investigate in vitro the anti-inflammatory effects of glaucolide B. Thus, an optimized washing extractive process performed on L. chamissonis leaves allowed to obtain a SL enriched extract (4.11â¯g). After a successful defatting pretreatment of the crude extract, the glaucolide B enriched ethyl acetate portion (2.00â¯g) was fractionated by CPC affording, in a single-step isolation, compound 1 (1.04â¯g) in great yield (25%) and purity (97%). Cytotoxicity effect of 1 on RAW 264.7 macrophages was determined by using MTT assay, revealing a CC10 of 14.11 µM. Compound 1 at 1, 3 and 10 µM inhibited the nitrite/nitrate (NOx) metabolites production and the pro-inflammatory interleukin 6 (IL-6) secretion on lipopolysaccharide-stimulated RAW 264.7 cells. The extractive process used turned to be selective for SL and CPC technique proved a simple and effective tool for the isolation of 1 within few hours. Isolated for the first time from L. chamissonis leaves, glaucolide B presented a significant inhibitory effect on both NO and IL-6 secretion under non-toxic concentrations.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Asteraceae/química , Centrifugação/métodos , Cromatografia Líquida/métodos , Sesquiterpenos/isolamento & purificação , Animais , Anti-Inflamatórios/farmacologia , Morte Celular/efeitos dos fármacos , Interleucina-6/biossíntese , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Extratos Vegetais/química , Folhas de Planta/química , Células RAW 264.7 , Sesquiterpenos/farmacologiaRESUMO
BACKGROUND: Deoxymikanolide is a sesquiterpene lactone isolated from Mikania micrantha and M. variifolia which, has previously demonstrated in vitro activity on Trypanosoma cruzi and in vivo activity on an infected mouse model. PURPOSE: Based on these promising findings, the aim of this study was to investigate the mechanism of action of this compound on different parasite targets. METHODS: The interaction of deoxymikanolide with hemin was examined under reducing and non- reducing conditions by measuring modifications in the Soret absorption band of hemin; the thiol interaction was determined spectrophotometrically through its reaction with 5,5'-dithiobis-2-nitrobenzoate in the presence of glutathione; activity on the parasite antioxidant system was evaluated by measuring the activity of the superoxide dismutase and trypanothione reductase enzymes, together with the intracellular oxidative state by flow cytometry. Superoxide dismutase and trypanothione reductase activities were spectrophotometrically tested. Cell viability, phosphatidylserine exposure and mitochondrial membrane potential were assessed by means of propidium iodide, annexin-V and rhodamine 123 staining, respectively; sterols were qualitatively and quantitatively tested by TLC; ultrastructural changes were analyzed by transmission electron microscopy. Autophagic cells were detected by staining with monodansylcadaverine. RESULTS: Deoxymikanolide decreased the number of reduced thiol groups within the parasites, which led to their subsequent vulnerability to oxidative stress. Treatment of the parasites with the compound produced a depolarization of the mitochondrial membrane even though the plasma membrane permeabilization was not affected. Deoxymikanolide did not affect the intracellular redox state and so the mitochondrial dysfunction produced by this compound could not be attributed to ROS generation. The antioxidant defense system was affected by deoxymikanolide at twenty four hours of treatment, when both an increased oxidative stress and decreased activity of superoxide dismutase and trypanothione reductase (40 and 60% respectively) were observed. Both the oxidative stress and mitochondrial dysfunction induce parasite death by apoptosis and autophagy. CONCLUSION: Based on our results, deoxymikanolide would exert its anti-T cruzi activity as a strong thiol blocking agent and by producing mitochondrial dysfunction.
Assuntos
Lactonas/farmacologia , Sesquiterpenos de Germacrano/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Glutationa/metabolismo , Hemina/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mikania/química , NADH NADPH Oxirredutases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Esteróis/biossíntese , Superóxido Dismutase/metabolismo , Trypanosoma cruzi/patogenicidade , Trypanosoma cruzi/ultraestruturaRESUMO
The title compound, erioflorin, C19H24O6 [systematic name: (1aR,3S,4Z,5aR,8aR,9R,10aR)-1a,2,3,5a,7,8,8a,9,10,10a-deca-hydro-3-hy-droxy-4,10a-dimethyl-8-methyl-idene-7-oxooxireno[5,6]cyclo-deca-[1,2-b]furan-9-yl methacrylate], is a tricyclic germacrane sesquiterpene lactone, which was isolated from Podanthus mitiqui (L.). The compound crystallizes in the space group P212121, and its mol-ecular structure consists of a methacrylic ester of a ten-membered ring sesquiterpenoid annelated with an epoxide and a butyrolactone. The structure is stabilized by one intramolecular C-Hâ¯O hydrogen bond. An O-Hâ¯O hydrogen bond and further C-Hâ¯O interactions can be observed in the packing.
RESUMO
A procura por novas substâncias com ação bactericida vem aumentando, devido à crescente resistência bacteriana às drogas utilizadas no tratamento de várias enfermidades. As plantas sintetizam compostos secundários com o intuito de se defender de condições ambientais adversas e estes podem ter atividade no controle de alguns micro-organismos. A maioria das asteraceas sintetiza lactonas sesquiterpênicas, compostos que vêm sendo estudados quanto à atividade bactericida. Sendo assim este trabalho teve como objetivo avaliar a ação bactericida do extrato bruto de duas espécies de asteraceae: Helianthus tuberosus e Smallanthus sonchifolius. Os ensaios de sensibilidade foram realizados com a incorporação dos dois extratos brutos em diferentes concentrações em agar e posterior semeadura das bactérias Staphylococcus aureus e Escherichia coli. Os resultados demonstraram que ambos os extratos apresentaram atividade de inibição total sobre o crescimento S. aureus e parcial sobre o crescimento de E. coli.
The search for new antibacterial substances has increased mainly due to higher bacterial resistance to the drugs commonly used for the treatment of diverse diseases. Plants synthesize secondary compounds as a defense mechanism against adverse environmental conditions. These substances may act on the growth or development of some microorganisms. Most Asteraceae plants synthesize sesquiterpenic lactones. These compounds have been studied for bactericidal activity. The objective of this study was to evaluate the bactericidal action of the crude extract of two species of Asteraceae: Helianthus tuberosus and Smallanthus sonchifolius. Sensitivity tests were performed with the incorporation of the two plant crude extracts at different concentrations in agar followed by the inoculation of S. aureus and E. coli bacteria. The results demonstrated that both extracts showed total inhibition activity over the growthof S. aureus and partial inhibition activity over the growth of E. coli.
Assuntos
Asteraceae/química , Lactonas/análise , Antibacterianos/análiseRESUMO
Lychnopholide is a sesquiterpene lactone usually obtained from Lychnophora and Eremanthus species and has pharmacological activities that include anti-inflammatory and anti-tumor. Lychnopholide isolated from Eremanthus matogrossenssis was analyzed in this study. The aims of this study were to develop and validate an analytical methodology by LC-MS/MS and to quantify lychnopholide in rat plasma. Chromatographic separation was achieved on a C18 column using isocratic elution with the mobile phase consisting of methanol and water (containing 0.1% formic acid) at a flow rate of 0.4 mL/min. The detection was performed in multiple-reaction monitoring mode using electrospray ionization in positive mode. The method validation was performed in accordance with regulatory guidelines and the results met the acceptance criteria. The linear range of detection was 10-200 ng/mL (r > 0.9961). The intra- and inter-day assay variability were <6.2 and <11.7%, respectively. The extraction recovery was approximately 63% using liquid-liquid extraction with chloroform. Lychnopholide was detected in plasma up to 60 min after intravenous administration in rats. This rapid and sensitive method for the analysis of the sesquiterpene lactone lychnopholide in rat plasma can be applied to pharmacokinetic studies of this compound. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Cromatografia Líquida/métodos , Lactonas/sangue , Sesquiterpenos/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Lactonas/farmacocinética , Limite de Detecção , Ratos , Reprodutibilidade dos Testes , Sesquiterpenos/farmacocinéticaRESUMO
The search for new antibacterial substances has increased mainly due to higher bacterial resistance to the drugs commonly used forthe treatment of diverse diseases. Plants synthesize secondary compounds as a defense mechanism against adverse environmental conditions. These substances may act on the growth or development of some microorganisms. Most Asteraceae plants synthesize sesquiterpenic lactones. These compounds have been studied for bactericidal activity. The objective of this study was to evaluate the bactericidal action of the crude extract of two species of Asteraceae: Helianthus tuberosus and Smallanthus sonchifolius. Sensitivity tests were performed with the incorporation of the two plant crude extracts at different concentrations in agar followed by the inoculation of S. aureus and E. coli bacteria. The results demonstrated that both extracts showed total inhibition activity over the growth of S. aureus and partial inhibition activity over the growth of E. coli.
A procura por novas substâncias com ação bactericida vem aumentando, devido à crescente resistência bacteriana às drogas utilizadas no tratamento de várias enfermidades. As plantas sintetizam compostos secundários com o intuito de se defender de condições ambientais adversas e estes podem ter atividade no controle de alguns micro-organismos. A maioria das asteraceas sintetiza lactonas sesquiterpênicas, compostos que vêm sendo estudados quanto à atividade bactericida. Sendo assim este trabalho teve como objetivo avaliar a ação bactericida do extrato bruto de duas espécies de asteraceae: Helianthus tuberosus e Smallanthus sonchifolius. Os ensaios de sensibilidade foram realizados com a incorporação dos dois extratos brutos em diferentes concentrações em agar e posterior semeadura das bactérias Staphylococcus aureus e Escherichia coli. Os resultados demonstraram que ambos os extratos apresentaram atividade de inibição total sobre o crescimento S. aureus e parcial sobre o crescimento de E. coli.
RESUMO
The title compound, dendocarbin A [systematic name: (1R,5aS,9aS,9bR)-1-hydroxy-6,6,9a-trimethyldodecahydronaphtho[1,2-c]furan-3-one], C15H22O3, is a sesquiterpene lactone isolated from Drimys winteri var chilensis. The monoclinic phase described herein displays an identical molecular structure to the orthorhombic phase that we reported previously [Paz Robles et al. (2014). Acta Cryst. C70, 1007-1010], while varying significantly in chain pitch, and can thus be considered as a borderline case of one-dimensional isostructural polymorphism.
Assuntos
Drimys/química , Lactonas/química , Sesquiterpenos/química , Cristalização , Lactonas/isolamento & purificação , Estrutura Molecular , Sesquiterpenos/isolamento & purificaçãoRESUMO
The natural compound dendocarbin A, C15H22O3, is a sesquiterpene lactone isolated for the first time from Drimys winteri for var chilensis. The compound crystallizes in the orthorhombic space group P212121 and its X-ray crystal structure confirmed the S/R character of the chiral centres at C-5/C-10 and C-9/C-11, respectively. The α-OH group at C-11 was found to be involved in intermolecular hydrogen bonding, defining chains along the <100> 21 screw axis.
Assuntos
Drimys/química , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Cristalografia por Raios X , Drimys/metabolismo , Estrutura Molecular , Sesquiterpenos/síntese químicaRESUMO
Entamoeba histolytica is the causative agent of human amoebiasis, which mainly affects developing countries. Although several drugs are effective against E. histolytica trophozoites, the control of amoebiasis requires the development of new and better alternative therapies. Medicinal plants have been the source of new molecules with remarkable antiprotozoal activity. Incomptine A isolated from Decachaeta incompta leaves, is a sesquiterpene lactone of the heliangolide type which has the major in vitro activity against E. histolytica trophozoites. However the molecular mechanisms involved in its antiprotozoal activity are still unknown. Using a proteomic approach based on two-dimensional gel electrophoresis and mass spectrometry (ESI-MS/MS) analysis, we evidenced that 21 E. histolytica proteins were differentially expressed in response to incomptine A treatment. Notably, three glycolytic enzymes, namely enolase, pyruvate:ferredoxin oxidoreductase and fructose-1,6-biphosphate aldolase, were down-regulated. Moreover, ultrastructural analysis of trophozoites through electronic microscopy showed an increased number of glycogen granules. Taken together, our data suggested that incomptine A could affect E. histolytica growth through alteration of its energy metabolism.
Assuntos
Asteraceae/química , Metabolismo Energético/efeitos dos fármacos , Entamoeba histolytica/efeitos dos fármacos , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Western Blotting , Regulação para Baixo , Disenteria Amebiana/tratamento farmacológico , Eletroforese em Gel Bidimensional , Entamoeba histolytica/metabolismo , Entamoeba histolytica/ultraestrutura , Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glicogênio/metabolismo , Humanos , Concentração Inibidora 50 , Lactonas/isolamento & purificação , Microscopia Eletrônica de Transmissão , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta/química , Plantas Medicinais/química , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Sesquiterpenos/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em TandemRESUMO
Estudou-se o efeito terapêutico da lactona sesquiterpênica (SL), 4,15-Epoxy-miller-9-Z-enolide, na lesão local do envenenamento botrópico experimental. Utilizaram-se três grupos de coelhos inoculados com 1.0µg de veneno de Bothrops alternatus e tratados com solução NaCl (0,85%) (grupo I), SL diluída em glicerol (0,5%) (grupo II) e SL diluída em vaselina (0,5%) (grupo III). Todos os animais foram avaliados nos tempos 30min e 1, 2, 24, 30, 48, 54, 72, 96, 120 e 148h quanto ao grau de edema, diâmetro do halo hemorrágico e presença de necrose local. Os animais do grupo II apresentaram os menores valores de grau de edema e halo hemorrágico com desaparecimento em 54h. Apesar de a necrose ter ocorrido em todos os animais, o diâmetro também foi menor no grupo II, quando comparado com os outros grupos. A SL, extraída da Milleria quinqueflora, possui efeito antiinflamatório, que é importante no tratamento local do envenenamento botrópico.(AU)