RESUMO
This work evaluated the volatile composition, antioxidant and antiprotozoal activities of the essential oil obtained from leaves of Eugenia gracillima Kiaersk. (EGEO) grown in Brazilian Northeast area (Araripe, Brazil). The volatile compounds of EGEO were analyzed by GC and GC-MS and its chemical composition is mainly composed of sesquiterpene hydrocarbons (91.22%), oxygenated sesquiterpenes (7.45%) and monoterpene (1.01%). The most abundant volatile constituents of the EGEO were germacrene D (16.10%), γ-muurolene (15.60%), bicyclogermacrene (8.53%), germacrene B (7.43%), and Δ-elemene (6.06%). The oil showed weak to moderate antioxidant activity. EGEO was highly selective to Leishmania braziliensis and Leishmania infantum promastigotes with selective indexes of 73.66 and 71.41, respectively. EGEO did not inhibit Trypanosoma cruzi. These data suggest that the E. gracillima essential oil is a relevant source of lead compounds for development of anti-Leishmania drugs.
Assuntos
Antioxidantes/farmacologia , Antiprotozoários/farmacologia , Eugenia/química , Óleos Voláteis/farmacologia , Folhas de Planta/química , Animais , Anti-Infecciosos/análise , Antiprotozoários/química , Linhagem Celular , Leishmania/efeitos dos fármacos , Camundongos , Óxido Nítrico/metabolismo , Óleos Voláteis/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologia , Superóxidos/metabolismo , Trypanosoma cruzi/efeitos dos fármacosRESUMO
The intensive application of agrochemicals in crops has negatively impacted the environment and other organisms. The use of naturally occurring compounds may be an alternative to mitigate these effects. Plants are secondary metabolite reservoirs and may present allelopathic activity, which is potentially interesting to be used in bioherbicide formulations. In this context, the present work aimed to evaluate the phytotoxic and cytotoxic effects of essential oils extracted from leaves of Sparattanthelium botocudorum and Sparattanthelium tupiniquinorum in bioassays with the plant models Lactuca sativa L. and Sorghum bicolor L. Moench. The essential oils were applied at concentrations of 3,000, 1,500, 750, 375 and 187.5 ppm. Chemical characterization of the oils was performed, and their impact on the percentage of germinated seeds, initial development of L. sativa and S. bicolor seedlings, and changes in the mitotic cycle of meristematic cells from L. sativa roots was evaluated. The major compound of the essential oils was germacrene D, followed by bicyclogermacrene, ß-elemene and germacrene A. The phytotoxicity assay showed that the essential oils of both species reduced the root and shoot growth in L. sativa and decreased the germination and shoot growth in S. bicolor. Inhibition was dependent on the tested oil concentration. In the cytotoxicity assay, a decrease in mitotic index and chromosomal and nuclear alterations were observed, which resulted from aneugenic and clastogenic action.
Assuntos
Hernandiaceae/metabolismo , Óleos Voláteis/química , Plântula/efeitos dos fármacos , Compostos Orgânicos Voláteis/farmacologia , Cromatografia Gasosa , Germinação/efeitos dos fármacos , Hernandiaceae/química , Lactuca/efeitos dos fármacos , Lactuca/crescimento & desenvolvimento , Mitose/efeitos dos fármacos , Óleos Voláteis/análise , Óleos Voláteis/farmacologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimento , Sesquiterpenos de Germacrano/farmacologia , Sorghum/efeitos dos fármacos , Sorghum/crescimento & desenvolvimento , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/químicaRESUMO
The need for effective candidates as cytotoxic drugs that at the same time challenge cancer multidrug resistance encouraged a search for these in plants of central Argentina. Bioassay-guided fractionation of the cytotoxic extract from Dimerostemma aspilioides led to the isolation of the germacranolide tomenphantin A (1), along with three new analogues (2-4). These efficiently inhibited the proliferation of the leukemia cell lines K562 and CCRF-CEM and their resistant variants, Lucena 1 and CEM/ADR5000, respectively, with IC50 values ranging from 0.40 to 7.7 µM. The structures and relative configurations of compounds 1-4 were elucidated by analysis of the spectroscopic data, in particular NMR spectroscopy. The most active among these was compound 1 (IC50 = 0.40-5.1 µM), and, therefore, this was selected as a model for a mechanistic study, which revealed that its antiproliferative effect was mediated by cell cycle arrest in the G2/M phase followed by apoptosis. The activity of compound 1 was selective, given the absence of cytotoxicity toward peripheral blood mononuclear cells. The results show the potential of these compounds, and in particular of compound 1, as leads for the development of drug candidates to fight sensitive and resistant leukemia cells.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Lactonas/farmacologia , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologia , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/ultraestrutura , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Monócitos/efeitos dos fármacos , Componentes Aéreos da Planta/química , Extratos Vegetais/químicaRESUMO
Peptic ulcers are currently treated with various drugs, all having serious side effects. The aim of this study was to evaluate the gastroprotective activity of calein D (from Calea urticifolia), a sesquiterpene lactone with a germacrane skeleton. Gastric lesions were induced in mice by administering ethanol (0.2 mL) after oral treatment with calein D at 3, 10 and 30 mg/kg, resulting in 13.15 ± 3.44%, 77.65 ± 7.38% and 95.76 ± 2.18% gastroprotection, respectively, to be compared with that of the control group. The effect found for 30 mg/kg of calein D was not reversed by pretreatment with NG-nitro-l-arginine methyl ester (l-NAME, 70 mg/kg, ip), indomethacin (10 mg/kg, sc) or N-ethylmaleimide (NEM, 10 mg/kg, sc). Hence, the mechanism of action of calein D does not involve NO, prostaglandins or sulfhydryl compounds. Calein D was more potent than carbenoxolone, the reference drug. The findings for the latter are in agreement with previous reports.
Assuntos
Asteraceae/química , Etanol/efeitos adversos , Lactonas/administração & dosagem , Sesquiterpenos de Germacrano/administração & dosagem , Úlcera Gástrica/prevenção & controle , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etilmaleimida/administração & dosagem , Etilmaleimida/farmacologia , Indometacina/administração & dosagem , Indometacina/farmacologia , Lactonas/química , Lactonas/farmacologia , Camundongos , Estrutura Molecular , NG-Nitroarginina Metil Éster/administração & dosagem , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Prostaglandinas/metabolismo , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Compostos de Sulfidrila/metabolismoRESUMO
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
Aiming detection of circadian variation in the chemical composition of volatiles from Piper regnellii, the leaves were collected during four different periods (8, 12, 16 and 20 h) in the same day. After extraction by hydrodistillation and GC/MS analysis, no significant variation was observed for the main compounds: germacrene D (45.6 ± 1.5-51.4 ± 3.1%), α-chamigrene (8.9 ± 1.3-11.3 ± 2.7%) and ß-caryophyllene (8.2 ± 0.9-9.5 ± 0.3%). Evaluation of in vitro cytotoxicity against several cancer and non-tumourigenic cells indicated promising activity, especially to HeLa (human cervical carcinoma) with IC50 ranging from 11 ± 3 to 17 ± 3 µg/mL. The obtained volatile oils were pooled and subjected to fractionation to afford pure ß-caryophyllene, α-chamigrene and germacrene D, being this last compound the more active against HeLa cells with IC50 of 7 ± 1 µg/mL (34 ± 5 µM). Therefore, the predominance of germacrene D in all analysed oils could justify, at least in part, the activity observed for the volatile compounds from P. regnellii leaves.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Relógios Circadianos/fisiologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Piper/química , Animais , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Cromatografia Gasosa-Espectrometria de Massas , Células HeLa , Humanos , Concentração Inibidora 50 , Camundongos , Extratos Vegetais/química , Folhas de Planta/química , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Sesquiterpenos Policíclicos , Sesquiterpenos/análise , Sesquiterpenos de Germacrano/análise , Sesquiterpenos de Germacrano/farmacologiaRESUMO
BACKGROUND: Leishmaniasis and Chagas disease are life-threatening illnesses caused by the protozoan parasites Leishmania spp. and Trypanosoma cruzi, respectively. They are known as "neglected diseases" due to the lack of effective drug treatments and the scarcity of research work devoted to them. Therefore, the development of novel and effective drugs is an important and urgent need. Natural products are an important source of bioactive molecules for the development of new drugs. In this study, we evaluated the activity of enhydrin, uvedalin and polymatin B, three sesquiterpene lactones (STLs) isolated from Smallanthus sonchifolius, on Leishmania mexicana (MNYC/BZ/62/M) and Trypanosoma cruzi (Dm28c). In addition, the in vivo trypanocidal activity of enhydrin and uvedalin and the effects of these STLs on parasites' ultrastructure were evaluated. METHODS: The inhibitory effect of the three STLs on the growth of L. mexicana amastigotes and promastigotes as well as T. cruzi epimastigotes was evaluated in vitro. The changes produced by the STLs on the ultrastructure of parasites were examined by transmission electron microscopy (TEM). Enhydrin and uvedalin were also studied in a murine model of acute T. cruzi infection (RA strain). Serum activities of the hepatic enzymes alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were used as biochemical markers of hepatotoxicity. RESULTS: The three compounds exhibited leishmanicidal activity on both parasite forms with IC50 values of 0.42-0.54 µg/ml for promastigotes and 0.85-1.64 µg/ml for intracellular amastigotes. Similar results were observed on T. cruzi epimastigotes (IC50 0.35-0.60 µg/ml). The TEM evaluation showed marked ultrastructural alterations, such as an intense vacuolization and mitochondrial swelling in both L. mexicana promastigotes and T. cruzi epimastigotes exposed to the STLs. In the in vivo study, enhydrin and uvedalin displayed a significant decrease in circulating parasites (50-71%) and no signs of hepatotoxicity were detected. CONCLUSIONS: Enhydrin, uvedalin and polymatin B possess significant leishmanicidal and trypanocidal activity on different parasite stages. These results show that these compounds may provide valuable leads for the development of new drugs against these neglected parasitic diseases.
Assuntos
Lactonas/farmacologia , Leishmania mexicana/efeitos dos fármacos , Sesquiterpenos de Germacrano/química , Sesquiterpenos/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Asteraceae/química , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Modelos Animais de Doenças , Lactonas/administração & dosagem , Lactonas/efeitos adversos , Lactonas/uso terapêutico , Leishmania mexicana/crescimento & desenvolvimento , Leishmania mexicana/ultraestrutura , Leishmaniose/tratamento farmacológico , Leishmaniose/parasitologia , Fígado/efeitos dos fármacos , Camundongos , Microscopia Eletrônica de Transmissão , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sesquiterpenos/administração & dosagem , Sesquiterpenos/efeitos adversos , Sesquiterpenos/química , Sesquiterpenos/uso terapêutico , Sesquiterpenos de Germacrano/farmacologia , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/ultraestruturaRESUMO
Four sesquiterpene lactones, mikanolide, deoxymikanolide, dihydromikanolide and scandenolide, were isolated by a bioassay-guided fractionation of Mikania variifolia and Mikania micrantha dichloromethane extracts. Mikanolide and deoxymikanolide were the major compounds in both extracts (2.2% and 0.4% for Mikania variifolia and 21.0% and 6.4% for Mikania micrantha respectively, calculated on extract dry weight). Mikanolide, deoxymikanolide and dihydromikanolide were active against Trypanosoma cruzi epimastigotes (50% inhibitory concentrations of 0.7, 0.08 and 2.5 µg/mL, for each compound respectively). These sesquiterpene lactones were also active against the bloodstream trypomastigotes (50% inhibitory concentrations for each compound were 2.1, 1.5 and 0.3 µg/mL, respectively) and against amastigotes (50% inhibitory concentrations for each compound were 4.5, 6.3 and 8.5 µg/mL, respectively). By contrast, scandenolide was not active on Trypanosoma cruzi. Besides, mikanolide and deoxymikanolide were also active on Leishmania braziliensis promastigotes (50% inhibitory concentrations of 5.1 and 11.5 µg/mL, respectively). The four sesquiterpene lactones were tested for their cytotoxicity on THP 1 cells. Deoxymikanolide presented the highest selectivity index for trypomastigotes (SI = 54) and amastigotes (SI = 12.5). In an in vivo model of Trypanosoma cruzi infection, deoxymikanolide was able to decrease the parasitemia and the weight loss associated to the acute phase of the parasite infection. More importantly, while 100% of control mice died by day 22 after receiving a lethal T. cruzi infection, 70% of deoxymikanolide-treated mice survived. We also observed that this compound increased TNF-α and IL-12 production by macrophages, which could contribute to control T. cruzi infection.
Assuntos
Lactonas/farmacologia , Leishmania braziliensis/efeitos dos fármacos , Mikania/química , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Descoberta de Drogas , Interleucina-12/biossíntese , Interleucina-12/imunologia , Lactonas/administração & dosagem , Lactonas/química , Lactonas/isolamento & purificação , Lactonas/uso terapêutico , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos de Germacrano/administração & dosagem , Sesquiterpenos de Germacrano/isolamento & purificação , Sesquiterpenos de Germacrano/farmacologia , Sesquiterpenos de Germacrano/uso terapêutico , Trypanosoma cruzi/isolamento & purificação , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologiaRESUMO
OBJECTIVES: The aims of this study were to investigate the chemical composition and the antioxidant activity and antibacterial activity of the essential oil of Xylopia sericea fruits (OXS). The fruits of this species are popularly used for medicinal purposes, and as a condiment in food preparation. METHODS: The chemical composition of OXS was analysed by GC/MS. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging, ß-carotene/linoleic acid bleaching and phosphomolybdenum and thiobarbituric acid-reactive substance (TBARS) assays were used to evaluate the antioxidant activity. Antibacterial activity was assessed by minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against bacterial strains of interest to human health and food spoilage. KEY FINDINGS: Eighty-four compounds were identified. The sesquiterpenes spathulenol (16.42%), guaiol (13.93%) and germacrene D (8.11%) were the most abundant constituents. OXS presented a significant antioxidant activity and also a high bacteriostatic effect against Staphylococcus aureus, Enterobacter cloacae, Bacillus cereus and Klebsiella pneumoniae. CONCLUSIONS: Those results evidenced the potential of OXS to treat human bacterial infections and as an antimicrobial ingredient for food preservation.
Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Frutas/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Xylopia/química , Antibacterianos/química , Antioxidantes/química , Bactérias/efeitos dos fármacos , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Brasil , Testes de Sensibilidade Microbiana/métodos , Óleos Voláteis/química , Picratos/química , Picratos/farmacologia , Extratos Vegetais/química , Óleos de Plantas/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologia , Sesquiterpenos de GuaianoRESUMO
Annona vepretorum Mart. (Annonaceae), popularly known as 'bruteira', has nutritional and medicinal uses. This study investigated the chemical composition and antitumour potential of the essential oil of A. vepretorum leaf alone and complexed with ß-cyclodextrin in a microencapsulation. The essential oil was obtained by hydrodistillation using a Clevenger-type apparatus and analysed using GC-MS and GC-FID. In vitro cytotoxicity of the essential oil and some of its major constituents in tumour cell lines from different histotypes was evaluated using the alamar blue assay. Furthermore, the in vivo efficacy of essential oil was demonstrated in mice inoculated with B16-F10 mouse melanoma. The essential oil included bicyclogermacrene (35.71%), spathulenol (18.89%), (E)-ß-ocimene (12.46%), α-phellandrene (8.08%), o-cymene (6.24%), germacrene D (3.27%) and α-pinene (2.18%) as major constituents. The essential oil and spathulenol exhibited promising cytotoxicity. In vivo tumour growth was inhibited by the treatment with the essential oil (inhibition of 34.46%). Importantly, microencapsulation of the essential oil increased in vivo tumour growth inhibition (inhibition of 62.66%).
Assuntos
Annona/química , Antineoplásicos Fitogênicos/farmacologia , Melanoma Experimental/tratamento farmacológico , Óleos Voláteis/farmacologia , Monoterpenos Acíclicos , Adulto , Alcenos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Monoterpenos Bicíclicos , Linhagem Celular Tumoral , Monoterpenos Cicloexânicos , Cicloexanonas/farmacologia , Modelos Animais de Doenças , Composição de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Células Hep G2 , Humanos , Concentração Inibidora 50 , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monoterpenos/farmacologia , Óleos Voláteis/química , Folhas de Planta/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Germacrano/farmacologia , Terpenos/farmacologia , Adulto Jovem , beta-Ciclodextrinas/farmacologiaRESUMO
Duguetia gardneriana, popularly known in the Brazilian northeast as "jaquinha", is a species belonging to the family Annonaceae. The aim of this work was to assess the chemical composition and antitumor properties of the essential oil from the leaves of D. gardneriana in experimental models. The chemical composition of the essential oil was analyzed via gas chromatography-flame ionization detector and gas chromatography-mass spectrometry. In vitro cytotoxic activity was determined in cultured tumor cells, and in vivo antitumor activity was assessed in B16-F10-bearing mice. The identified compounds were ß-bisabolene (80.99%), elemicin (8.04%), germacrene D (4.15%), and cyperene (2.82%). The essential oil exhibited a cytotoxic effect, with IC50 values of 16.89, 19.16, 13.08, and 19.33 µg/mL being obtained for B16-F10, HepG2, HL-60, and K562 cell lines, respectively. On the other hand, ß-bisabolene was inactive in all of the tested tumor cell lines (showing IC50 values greater than 25 µg/mL). The in vivo analysis revealed tumor growth inhibition rates of 5.37-37.52% at doses of 40 and 80 mg/kg/day, respectively. Herein, the essential oil from the leaves of D. gardneriana presented ß-bisabolene as the major constituent and showed cytotoxic and antitumor potential.
Assuntos
Annonaceae/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Óleos Voláteis/farmacologia , Adulto , Animais , Linhagem Celular Tumoral/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Sesquiterpenos Monocíclicos , Óleos Voláteis/química , Folhas de Planta/química , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Pirogalol/análogos & derivados , Pirogalol/química , Pirogalol/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Germacrano/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
CONTEXT: Nectandra (Lauraceae) species have been used in folk medicine as an antidiarrheal, analgesic, antifungal, etc., and have many pharmacological proprieties. OBJECTIVE: Investigation of the chemical composition and cytotoxicity of essential oil from Nectandra leucantha Nees & Mart. leaves. This is the first study involving N. leucantha reported in the literature. MATERIAL AND METHODS: The essential oil of N. leucantha leaves was obtained by hydrodistillation. Its chemical composition was determined using a combination of GC/FID, GC/MS, and determination of Kovats index (KI). In vitro cytotoxic activity was evaluated against six cancer cell lines - murine melanoma (B16F10-Nex2), human glioblastome (U-87), human cervical carcinoma (HeLa), human colon carcinoma (HCT), human breast adenocarcinoma (MCF7), and human cervical tumor (Siha) as well as against one non-tumorigenic cell line - human foreskin fibroblast (HFF). RESULTS: Thirty-three compounds were identified primarily sesquiterpenes (81.41%), the main compounds being bicyclogermacrene (28.44%), germacrene A (7.34%), spathulenol (5.82%), and globulol (5.25%). Furthermore, monoterpenes were also found in the analyzed oil (12.84%), predominantly α- and ß-pinenes (6.59 and 4.57%, respectively). The crude essential oil displayed significant cytotoxic activity against B16F10-Nex2 (IC50 33 ± 1 µg/mL) and U87 (IC50 75.95 ± 0.03 µg/mL) and HeLa (IC50 60 ± 12 µg/mL) cell lines. The main identified compound, bicyclogermacrene, displayed IC50 ranging from 3.1 ± 0.2 to 21 ± 6 µg/mL. DISCUSSION AND CONCLUSION: The results indicate that the crude oils from leaves of N. leucantha displayed cytotoxic activity being bicyclogermacrene, the main compound identified in the crude oil responsible, at least in part, for this potential.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Lauraceae/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Compostos Bicíclicos com Pontes/química , Compostos Bicíclicos com Pontes/isolamento & purificação , Compostos Bicíclicos com Pontes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Estrutura Molecular , Óleos Voláteis/isolamento & purificação , Folhas de Planta/química , Óleos de Plantas/isolamento & purificação , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Sesquiterpenos de Germacrano/farmacologiaRESUMO
The sesquiterpene lactones (STLs) are a large class of plant secondary metabolites that are generally found in the Asteraceae family and that have high diversity with respect to chemical structure as well as biological activity. STLs have been classified into different groups, such as guaianolides, germacranolides, and melampolides etc., based on their carboxylic skeleton. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under the stimulus of progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. The purpose of this work was to determine whether sesquiterpene lactones from the germacranolide and melampolide groups act as inhibitor agents on the meiosis of amphibian oocytes in vitro. Results for germacranolides indicated that the addition of deoxyelephantopins caused a high degree of inhibition and that minimolide showed a moderate inhibitory effect, whereas glaucolide A was inactive. Furthermore, the addition of melampolides (uvedalin, enhydrin, polymatin A and polymatin B) showed inhibitory effects. For enhydrin and uvedalin, inhibitory effects were observed at the higher concentrations assayed. The results of this study suggest that the inhibitory activity of the tested sesquiterpene lactones on the meiosis of Rhinella arenarum oocytes is not dependent on the group to which they belong, i.e. not on the carboxylic skeleton, but probably due to the arrangement and type of function groups present in the molecules. All assayed lactones in the germacranolide group showed low toxicity. In contrast, important differences in toxicity were observed for lactones from the melampolide group: enhydrin and uvedalin showed low toxicity, but polymatin A and B were highly toxic.
Assuntos
Bufo arenarum , Técnicas de Maturação in Vitro de Oócitos/métodos , Lactonas/farmacologia , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Sesquiterpenos/farmacologia , Animais , Feminino , Progesterona/farmacologia , Sesquiterpenos de Germacrano/farmacologiaRESUMO
Five new sesquiterpenes, neurolobatin A (1), neurolobatin B (2), 5ß-hydroxy-8ß-isovaleroyloxy-9α-hydroxycalyculatolide (3), 3-epi-desacetylisovaleroylheliangine (4), and 3ß-acetoxy-8ß-isovaleroyloxyreynosin (5), were isolated from the aerial parts of Neurolaena lobata. The structures were established by means of a combined spectroscopic data analysis, including ESIMS, APCI-MS, and 1D- and 2D-NMR techniques. Neurolobatin A (1) and B (2) are unusual isomeric seco-germacranolide sesquiterpenes with a bicyclic acetal moiety, compounds 3 and 4 are unsaturated epoxy-germacranolide esters, and compound 5 is the first eudesmanolide isolated from the genus Neurolaena. The isolated compounds (1-5) were shown to have noteworthy antiproliferative activities against human tumor cell lines (A2780, A431, HeLa, and MCF7). The anti-inflammatory effects of 1-5, evaluated in vitro using LPS- and TNF-α-induced IL-8 expression inhibitory assays, revealed that all these compounds strongly down-regulated the LPS-induced production of IL-8 protein, with neurolobatin B (2) and 3-epi-desacetylisovaleroylheliangine (4) being the most effective.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Asteraceae/química , Sesquiterpenos de Germacrano/isolamento & purificação , Sesquiterpenos de Germacrano/farmacologia , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Guatemala , Células HeLa , Humanos , Interleucina-8/metabolismo , Lipopolissacarídeos/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Sesquiterpenos de Germacrano/química , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais/citologia , Veias Umbilicais/efeitos dos fármacosRESUMO
Xylopia laevigata, popularly known as "meiú" and "pindaíba", is a medicinal plant used in the folk medicine of the Brazilian Northeast for several purposes. The chemical constituents of the essential oil from leaves of X. laevigata, collected from wild plants growing at three different sites of the remaining Atlantic forest in Sergipe State (Brazilian Northeast), were analyzed by GC/FID and GC/MS. The effect of the essential oil samples was assessed on tumor cells in culture, as well on tumor growth in vivo. All samples of the essential oil were dominated by sesquiterpene constituents. A total of 44 compounds were identified and quantified. Although some small differences were observed in the chemical composition, the presence of γ-muurolene (0.60-17.99%), δ-cadinene (1.15-13.45%), germacrene B (3.22-7.31%), α-copaene (3.33-5.98%), germacrene D (9.09-60.44%), bicyclogermacrene (7.00-14.63%), and (E)-caryophyllene (5.43-7.98%) were verified as major constituents in all samples of the essential oil. In the in vitro cytotoxic study, the essential oil displayed cytotoxicity to all tumor cell lines tested, with the different samples displaying a similar profile; however, they were not hemolytic or genotoxic. In the in vivo antitumor study, tumor growth inhibition rates were 37.3-42.5%. The treatment with the essential oil did not significantly affect body weight, macroscopy of the organs, or blood leukocyte counts. In conclusion, the essential oil from the leaves of X. laevigata is chemically characterized by the presence of γ-muurolene, δ-cadinene, germacrene B, α-copaene, germacrene D, bicyclogermacrene, and (E)-caryophyllene as major constituents and possesses significant in vitro and in vivo anticancer potential.
Assuntos
Óleos Voláteis/química , Óleos Voláteis/farmacologia , Xylopia/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Brasil , Linhagem Celular Tumoral , Células Cultivadas , Eritrócitos/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Medicina Tradicional , Camundongos , Óleos Voláteis/análise , Folhas de Planta/química , Folhas de Planta/efeitos dos fármacos , Óleos de Plantas/análise , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Plantas Medicinais/química , Plantas Medicinais/efeitos dos fármacos , Sesquiterpenos Policíclicos , Sarcoma 180/tratamento farmacológico , Sarcoma 180/patologia , Sesquiterpenos/análise , Sesquiterpenos/farmacologia , Sesquiterpenos de Germacrano/farmacologiaRESUMO
In this study, the chemical composition and the in vitro schistosomicidal properties of the essential oil obtained from Bidens sulphurea flowers (Bs-EO) were investigated. Its major constituents were identified as being 2,6-di-tert-butyl-4-methylphenol (44.98%), germacrene D (33.70%) and ß-caryophyllene (10.23%). Bs-EO at 100 µg mL(-1) caused death of all the adult worms and promoted separation of the couple pairs into individual male and female within 48 h, besides leading to a significant decrease in the motility of the parasites. This oil was also responsible for a remarkable reduction in the number of eggs and the percentage of developed eggs produced by adult worms. These results suggest that the Bs-EO can be considered a promising source for the development of new schistosomicidal agents.
Assuntos
Asteraceae/química , Flores/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Esquistossomicidas/química , Esquistossomicidas/farmacologia , Animais , Sesquiterpenos Policíclicos , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologiaRESUMO
The antibacterial activity of nine selected essential oils (EOs) against a panel of oral pathogens was investigated in terms of their minimum inhibitory concentrations (MICs) by using the broth microdilution method. Most of the EOs displayed weak activity or were inactive against the selected oral pathogens, with MIC values ranging from 500 to 4000 µg/mL. However, the EO obtained from the leaves of Bidens sulphurea (Asteraceae) was found to display moderate activity against Streptococcus mutans (MIC = 250 µg/mL) and significant activity against Streptococcus mitis (MIC = 31.25 µg/mL). Germacrene D (38.3%), trans-caryophyllene (18.0%), ß-elemene (13.9%) and bicyclogermacrene (13.1%) were identified as the main chemical components of this oil. 2,6-Di-tert-butyl-4-methylphenol, previously described as the major constituent in the EO from the flowers of B. sulphurea, was not detected in this study.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Asteraceae/química , Bactérias/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Sesquiterpenos Policíclicos , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologia , Streptococcus mutans/efeitos dos fármacosRESUMO
OBJECTIVE: The sesquiterpene, mikanolide, was found to possess antibacterial activity. As a result, a structure-activity relationship study was carried out on mikanolide and eleven of its derivatives. METHODS: Mikanolide and two of its derivatives were isolated from organic extract of Mikania micrantha using chromatographic methods. Nine additional derivatives were synthesized and all were investigated for their antibacterial activity against the Gram positive pathogen Staphylococcus aureus and beta haemolytic Streptococcus group A (BHSA) as well as the Gram negative Escherichia coli using the disk diffusion assay. RESULTS: The investigation revealed that only four of the derivatives displayed antibacterial activity and only pathogens Staphylococcus aureus and beta haemolytic Streptococcus group A were susceptible at a concentration of 100 µg per disk. However, there was an increase in activity for three of the derivatives in comparison to mikanolide. CONCLUSION: This study underscores the potential for phytochemicals from locally available plants to be further investigated and developed as antibacterial agents.
OBJETIVO: Se halló que el sesquiterpene - mikanolida - posee actividad antibacteriana. Como resultado, se llevó a cabo un estudio de la relación estructura-actividad de la mikanolida y once de sus derivados. MÉTODOS: La mikanolida y dos de sus derivados fueron aislados a partir de un extracto orgánico de Mikania micrantha, mediante métodos cromatográficos. Se sintetizaron otros nueve derivados adicionales, y se investigó la actividad antibacteriana de todos sobre el patógeno Gram positivo Staphylococcus aureus y el Streptococcus beta hemolítico grupo A (BHSA) así como Escherichia coli Gram negativo, usando el ensayo de difusión en disco. RESULTADOS: La investigación reveló que sólo cuatro de los derivados mostraban actividad antibacteriana y sólo los patógenos Staphylococcus aureus y Streptococcus beta hemolítico grupo A eran susceptibles a una concentración de 100 µg por disco. Sin embargo, se produjo un aumento en la actividad de tres de los derivados en comparación con la mikanolida. CONCLUSIÓN: Este estudio subraya el potencial que poseen los fotoquímicos a partir de plantas localmente disponibles, para ser objeto de investigación ulterior y ser desarrollados como agentes antibacterianos.
Assuntos
Humanos , Lactonas/farmacologia , Sesquiterpenos de Germacrano/farmacologia , Antibacterianos/farmacologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: The sesquiterpene, mikanolide, was found to possess antibacterial activity. As a result, a structure-activity relationship study was carried out on mikanolide and eleven of its derivatives. METHODS: Mikanolide and two of its derivatives were isolated from organic extract of Mikania micrantha using chromatographic methods. Nine additional derivatives were synthesized and all were investigated for their antibacterial activity against the Gram positive pathogen Staphylococcus aureus and beta haemolytic Streptococcus group A (BHSA) as well as the Gram negative Escherichia coli using the disk diffusion assay. RESULTS: The investigation revealed that only four of the derivatives displayed antibacterial activity and only pathogens Staphylococcus aureus and beta haemolytic Streptococcus group A were susceptible at a concentration of 100 microg per disk. However there was an increase in activity for three of the derivatives in comparison to mikanolide. CONCLUSION: This study underscores the potential for phytochemicals from locally available plants to be further investigated and developed as antibacterial agents.
Assuntos
Lactonas/farmacologia , Sesquiterpenos de Germacrano/farmacologia , Antibacterianos/farmacologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Humanos , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
The composition of the spasmolytic essential oil of the medicinal species Brickellia veronicaefolia was established by NMR spectroscopy in addition to GC-MS analysis and HPLC studies. Seven major compounds, representing ca. 86% of the oil, were identified as benzyl 2,6-dimethoxybenzoate (1), 2-hydroxybenzyl 2'-methoxybenzoate (2), chamazulene (3), beta-caryophyllene (4), germacrene D (5), bicyclogermacrene (6), and beta-eudesmol (7). A sensitive and accurate analytical 1H NMR method has been developed for the quantification of the major compounds in the essential oil of B. veronicaefolia. The method was validated using benzyl 2,6-dimethoxybenzoate (1) and beta-caryophyllene (4), two of the active principles in the oil, and successfully applied to the determination of these pharmacologically active compounds in three different batches of the oil collected in different geographical regions and/or seasons.