RESUMEN
Schistosomiasis, a widespread parasitic disease caused by the blood fluke of the genus Schistosoma, affects over 230 million people, primarily in developing countries. Praziquantel, the sole drug currently approved for schistosomiasis treatment, demonstrates effectiveness against patent infections. A recent study highlighted the antiparasitic properties of amiodarone, an anti-arrhythmic drug, exhibiting higher efficacy than praziquantel against prepatent infections. This study assessed the efficacy of amiodarone and praziquantel, both individually and in combination, against Schistosoma mansoni through comprehensive in vitro and in vivo experiments. In vitro experiments demonstrated synergistic activity (fractional inhibitory concentration index ≤0.5) for combinations of amiodarone with praziquantel. In a murine model of schistosomiasis featuring prepatent infections, treatments involving amiodarone (200 or 400 mg/kg) followed by praziquantel (200 or 400 mg/kg) yielded a substantial reduction in worm burden (60%-70%). Given the low efficacy of praziquantel in prepatent infections, combinations of amiodarone with praziquantel may offer clinical utility in the treatment of schistosomiasis.
Asunto(s)
Amiodarona , Praziquantel , Schistosoma mansoni , Esquistosomiasis mansoni , Amiodarona/farmacología , Amiodarona/uso terapéutico , Animales , Praziquantel/farmacología , Praziquantel/uso terapéutico , Schistosoma mansoni/efectos de los fármacos , Ratones , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/parasitología , Femenino , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Sinergismo Farmacológico , Quimioterapia Combinada , Masculino , Modelos Animales de EnfermedadRESUMEN
Schistosomiasis is a major neglected disease that imposes a substantial worldwide health burden, affecting approximately 250â million people globally. As praziquantel is the only available drug to treat schistosomiasis, there is a critical need to identify new anthelmintic compounds, particularly from natural sources. To enhance the activity of different natural products, one potential avenue involves its combination with silver nanoparticles (AgNP). Based on this approach, a one-step green method for the inâ situ preparation of dehydrodieugenol (DHDG) by oxidation coupling reaction using silver and natural eugenol is presented. AgNP formation was confirmed by UV-Vis spectroscopy due to the appearance of the surface plasmon resonance (SPR) band at 430â nm which is characteristic of silver nanoparticles. The nanoparticles were spherical with sizes in the range of 40 to 50â nm. Bioassays demonstrated that the silver nanoparticles loaded with DHDG exhibited significant anthelmintic activity against Schistosoma mansoni adult worms without toxicity to mammalian cells and an inâ vivo animal model (Caenorhabditis elegans), contributing to the development of new prototypes based on natural products for the treatment of schistosomiasis.
Asunto(s)
Antihelmínticos , Antiinfecciosos , Productos Biológicos , Eugenol/análogos & derivados , Lignanos , Nanopartículas del Metal , Esquistosomiasis , Animales , Humanos , Plata/farmacología , Plata/química , Nanopartículas del Metal/química , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Esquistosomiasis/tratamiento farmacológico , Antiinfecciosos/uso terapéutico , Schistosoma mansoni , Productos Biológicos/uso terapéutico , MamíferosRESUMEN
Baccharis mattogrosensis is a species from Asteraceae which has been used in Brazilian folk medicine to treatment of several illnesses, including those caused by parasites. In the present work, the MeOH extract of aerial parts of B. mattogrosensis was subjected to chromatographic fractionation to afford three flavonoids: apigenin (1), quercetin (2), and kaempferol (3) as well as a mixture three chlorogenic acids: 3,4-O-dicaffeoylquinic (4), 3,5-O-dicaffeoylquinic (5), and 4,5-O-dicaffeoylquinic (6) acids. When tested in vitro, kaempferol (3) exhibited activity against Schistosoma mansoni with EC50 = 81.86 µM, whereas compounds 1, 2, 4 - 6 showed to be inactives. Considering this result, the effects of kaempferol (3) against S. mansoni infection using in vivo assay was tested at first time. Using a single oral dose (400 mg/kg) of kaempferol (3) to S. mansoni-infected mice reduced the worm burden by 25.5%. Similarly, the number of eggs, which are responsible for a variety of pathologies and transmission of schistosomiasis, was decreased by 28.8% in treated mice. Collectively, although kaempferol (3) is partially active when administered orally in a mouse model of schistosomiasis, our results suggest that this compound could be, in future studies, administered in different forms, such as nanoformulation.
RESUMEN
Snake venoms are important sources of bioactive molecules, including those with antiparasitic activity. Cathelicidins form a class of such molecules, which are produced by a variety of organisms. Batroxicidin (BatxC) is a cathelicidin found in the venom of the common lancehead (Bothrops atrox). In the present work, BatxC and two synthetic analogues, BatxC(C-2.15Phe) and BatxC(C-2.14Phe)des-Phe1, were assessed for their microbicidal activity. All three peptides showed a broad-spectrum activity on Gram-positive and -negative bacteria, as well as promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Circular dichroism (CD) and nuclear magnetic resonance (NMR) data indicated that the three peptides changed their structure upon interaction with membranes. Biomimetic membrane model studies demonstrated that the peptides exert a permeabilization effect in prokaryotic membranes, leading to cell morphology distortion, which was confirmed by atomic force microscopy (AFM). The molecules considered in this work exhibited bactericidal and leishmanicidal activity at low concentrations, with the AFM data suggesting membrane pore formation as their mechanism of action. These peptides stand as valuable prototype drugs to be further investigated and eventually used to treat bacterial and protozoal infections.
Asunto(s)
Antibacterianos/farmacología , Péptidos Antimicrobianos/farmacología , Antiprotozoarios/farmacología , Bothrops , Venenos de Serpiente/química , Secuencia de Aminoácidos , Animales , Antibacterianos/química , Péptidos Antimicrobianos/química , Antiprotozoarios/química , Catelicidinas , Células Cultivadas , Leishmania/efectos de los fármacos , Macrófagos , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , América del SurRESUMEN
Schistosomiasis is a major public health problem that afflicts more than 240 million individuals globally, particularly in poor communities. Treatment of schistosomiasis relies heavily on a single oral drug, praziquantel, and there is interest in the search for new antischistosomal drugs. This study reports the anthelmintic evaluation of carvacryl acetate, a derivative of the terpene carvacrol, against Schistosoma mansoni ex vivo and in a schistosomiasis animal model harboring either adult (patent infection) or juvenile (prepatent infection) parasites. For comparison, data obtained with gold standard antischistosomal drug praziquantel are also presented. Initially in vitro effective concentrations of 50% (EC50) and 90% (EC90) were determined against larval and adult stages of S. mansoni. In an animal with patent infection, a single oral dose of carvacryl acetate (100, 200, or 400 mg/kg) caused a significant reduction in worm burden (30-40%). S. mansoni egg production, a process responsible for both life cycle and pathogenesis, was also markedly reduced (70-80%). Similar to praziquantel, carvacryl acetate 400 mg/kg had low efficacy in pre-patent infection. In tandem, although carvacryl acetate had interesting in vitro schistosomicidal activity, the compound exhibited low efficacy in terms of reduction of worm load in S. mansoni-infected mice.
Asunto(s)
Esquistosomiasis mansoni , Esquistosomicidas , Administración Oral , Animales , Ratones , Monoterpenos , Schistosoma mansoni , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomicidas/uso terapéuticoRESUMEN
Schistosomiasis, caused by a blood fluke of the genus Schistosoma, afflicts over 230 million people worldwide. Treatment of the disease relies on just one drug, praziquantel. Cnicin (Cn) is the sesquiterpene lactone found in blessed thistle (Centaurea benedicta) that showed antiparasitic activities but has not been evaluated against Schistosoma. However, cnicin has poor water solubility, which may limit its antiparasitic activities. To overcome these restrictions, inclusion complexes with cyclodextrins may be used. In this work, we evaluated the in vitro and in vivo antischistosomal activities of cnicin and its complexes with ß-cyclodextrin (ßCD) and 2-hydroxypropyl-ß-cyclodextrin (HPßCD) against Schistosoma mansoni. Cnicin were isolated from C. benedicta by chromatographic fractionation. Complexes formed by cnicin and ßCD (Cn/ßCD), as well as by cnicin and HPßCD (Cn/HPßCD), were prepared by coprecipitation and characterized. In vitro schistosomicidal assays were used to evaluate the effects of cnicin and its complexes on adult schistosomes, while the in vivo antischistosomal assays were evaluated by oral and intraperitoneal routes. Results showed that cnicin caused mortality and tegumental alterations in adult schistosomes in vitro, also showing in vivo efficacy after intraperitoneal administration. The oral treatment with cnicin or Cn/ßCD showed no significant worm reductions in a mouse model of schistosomiasis. In contrast, Cn/HPßCD complex, when orally or intraperitoneally administered to S. mansoni-infected mice, decreased the total worm load, and markedly reduced the number of eggs, showing high in vivo antischistosomal effectiveness. Permeability studies, using Nile red, indicated that HPßCD complex may reach the tegument of adult schistosomes in vivo. These results demonstrated the antischistosomal potential of cnicin in preparations with HPßCD.
Asunto(s)
Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomicidas/farmacología , Sesquiterpenos/farmacología , 2-Hidroxipropil-beta-Ciclodextrina , Administración Oral , Animales , Centaurea/química , Modelos Animales de Enfermedad , Composición de Medicamentos , Heces/parasitología , Femenino , Inyecciones Intraperitoneales , Masculino , Ratones , Recuento de Huevos de Parásitos , Carga de Parásitos , Permeabilidad , Praziquantel/farmacología , Praziquantel/uso terapéutico , Esquistosomiasis mansoni/parasitología , Esquistosomicidas/administración & dosificación , Esquistosomicidas/química , Esquistosomicidas/farmacocinética , Sesquiterpenos/administración & dosificación , Sesquiterpenos/química , Sesquiterpenos/farmacocinética , Solubilidad , beta-CiclodextrinasRESUMEN
Schistosomiasis is a widespread human parasitic disease currently affecting over 200 million people, particularly in poor communities. Chemotherapy for schistosomiasis relies exclusively on praziquantel (PZQ). Previous studies have shown that licarin A (LIC-A), a dihydrobenzofuran neolignan, exhibited in vitro antiparasitic activity against Schistosoma mansoni adult worms. This study aimed to investigate the potential of LIC-A, isolated as main metabolite from leaves of Nectandra oppositifolia Nees & Mart. (Lauraceae), as an antischistosomal agent orally active in schistosomiasis animal model. PZQ was used as a reference compound. As result, LIC-A showed, at a single dose of 400 mg/kg, to be able to partially cure infected mice (worm burden reductions of ~50%). Parasite eggs, that are responsible for a variety of pathologies and transmission of schistosomiasis, were also moderately inhibited by LIC-A (egg burden reductions of ~50%-60%). Furthermore, it was observed that LIC-A achieved a slight reduction of hepatomegaly and splenomegaly. Collectively, although LIC-A was partially active when administered orally, these results give support for the antiparasitic potential LIC-A as lead compound for novel antischistosomal agent.
Asunto(s)
Lauraceae , Lignanos , Esquistosomiasis mansoni , Animales , Lauraceae/química , Lignanos/farmacología , Ratones , Recuento de Huevos de Parásitos , Schistosoma mansoni , Esquistosomiasis mansoni/tratamiento farmacológicoRESUMEN
Infections caused by parasitic worms impose a considerable worldwide health burden. One of the most impactful is schistosomiasis, a disease caused by blood-dwelling of the genus Schistosoma that affects more than 230â million people worldwide. Since praziquantel has also been extensively used to treat schistosomiasis and other parasitic flatworm infections, there is an urgent need to identify novel anthelmintic compounds, mainly from natural sources. In this study, the hexane extract from roots of Piper malacophyllum (Piperaceae) showed to be mainly composed for gibbilimbolâ B by HPLC/ESI-HRMS. Based on this result, this compound was isolated by chromatographic steps and its structure was confirmed by NMR. Inâ vitro bioassays showed that gibbilimbolâ B was more active than praziquantel against larval stage of S.â mansoni, with effective concentrations of 50 % (EC50 ) and 90 % (EC90 ) values of 2.6 and 3.4â µM, respectively. Importantly, gibbilimbolâ B showed no cytotoxicity to mammalian cells at a concentration 190â times greater than the antiparasitic effect, giving support for the anthelmintic potential of gibbilimbolâ B as lead compound for novel antischistosomal agents.
Asunto(s)
Fenoles/farmacología , Piperaceae/química , Extractos Vegetales/farmacología , Schistosoma mansoni/efectos de los fármacos , Animales , Estructura Molecular , Fenoles/química , Fenoles/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/químicaRESUMEN
Schistosomiasis, a neglected tropical disease caused by Schistosoma species, harms over 250â million people in several countries. The treatment is achieved with only one drug, praziquantel. Cardamonin, a natural chalcone with inâ vitro schistosomicidal activity, has not been inâ vivo evaluated against Schistosoma. In this work, we evaluated the inâ vivo schistosomicidal activities of cardamonin against Schistosoma mansoni worms and conducted enzymatic apyrase inhibition assay, as well as molecular docking analysis of cardamonin against potato apyrase, S.â mansoni NTPDaseâ 1 and S.â mansoni NTPDaseâ 2. In a mouse model of schistosomiasis, the oral treatment with cardamonin (400â mg/kg) showed efficacy against S.â mansoni, decreasing the total worm load in 46.8 % and reducing in 54.5 % the number of eggs in mice. Cardamonin achieved a significant inhibition of the apyrase activity and the three-dimensional structure of the potato apyrase, obtained by homology modeling, showed that cardamonin may interact mainly through hydrogen bonds. Molecular docking studies corroborate with the action of cardamonin in binding and inhibiting both potato apyrase and S.â mansoni NTPDases.
Asunto(s)
Apirasa/antagonistas & inhibidores , Chalconas/farmacología , Inhibidores Enzimáticos/farmacología , Piperaceae/química , Extractos Vegetales/farmacología , Schistosoma mansoni/efectos de los fármacos , Animales , Apirasa/metabolismo , Biomphalaria , Chalconas/química , Chalconas/aislamiento & purificación , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Femenino , Ratones , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Solanum tuberosum/enzimologíaRESUMEN
Praziquantel is currently the only drug available to treat schistosomiasis, a disease of enormous public health significance caused by a blood fluke of the genus Schistosoma Diminazene, a drug approved by the FDA, has been successfully used to treat diseases caused by blood protozoan parasites. In this study, we evaluated the antiparasitic properties of diminazene against Schistosoma mansoniex vivo and in mice harboring either chronic or early S. mansoni infections. In vitro, we monitored phenotypic and tegumental changes as well as the effects of the drug on pairing and egg production. In mice infected with either adult (chronic infection) or immature (early infection) worms, diminazene was administered intraperitoneally (10 to 100 mg/kg of body weight) or by oral gavage (100 to 400 mg/kg), and we studied the influence of the drug on worm burden and egg production. Liver and spleen pathologies and serum aminotransferase levels were also analyzed. In vitro, 50% effective concentrations (EC50) and EC90 revealed that diminazene is able to kill both immature and adult parasites, and its effect was time and concentration dependent. In addition, confocal laser scanning microscopy showed morphological alterations in the teguments of schistosomes. In an animal model, the influence of the drug on worm burden, egg production, hepatomegaly, and splenomegaly depended on the dosing regimen applied and the route of administration. Diminazene also caused a significant reduction in aminotransferase levels. Comparatively, diminazene treatment was more effective in chronic infection than in early infection. In tandem, our study revealed that diminazene possesses anthelmintic properties and inhibits liver injury caused by Schistosoma eggs.
Asunto(s)
Parásitos , Esquistosomiasis mansoni , Esquistosomiasis , Animales , Diminazeno/análogos & derivados , Diminazeno/farmacología , Ratones , Schistosoma mansoni , Esquistosomiasis mansoni/tratamiento farmacológicoRESUMEN
Praziquantel is the only available drug to treat schistosomiasis, and therefore, urgent studies must be performed to identify new anthelmintic agents. This study reports the anthelmintic evaluation of two related ent-kaurane diterpenes isolated from aerial parts of Baccharis lateralis (Asteraceae), ent-kaur-16-en-19-oic acid (1) and 15ß-senecioyl-oxy-ent-kaur-16-en-19-oic acid (2) against Schistosoma mansoni in vitro and in a murine model of schistosomiasis. Both compounds exhibited in vitro activity with lethal concentration 50% (LC50) values of 26.1 µM (1) and 11.6 µM (2) as well as reduced toxicity against human cell lines, revealing a good selectivity profile, mainly with compound 2 (selectivity index > 10). Compound 2 also decreased egg production and caused morphological alterations in the parasite reproductive system. In mice infected with S. mansoni, oral treatment with compound 2 at 400 mg/kg, the standard dose used in this model of schistosomiasis, caused a significant reduction in a total worm burden of 61.9% (P < 0.01). S. mansoni egg production, a key mechanism for both transmission and pathogenesis, was also markedly reduced. In addition, compound 2 achieved a significant reduction in hepatosplenomegaly. Therefore, the diterpene 15ß-senecioyl-oxy-ent-kaur-16-en-19-oic acid (2) has an acceptable cytotoxicity profile and is orally active in a murine schistosomiasis model.
Asunto(s)
Baccharis/química , Diterpenos de Tipo Kaurano/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Esquistosomiasis/tratamiento farmacológico , Administración Oral , Animales , Diterpenos de Tipo Kaurano/administración & dosificación , Diterpenos de Tipo Kaurano/uso terapéutico , Humanos , RatonesRESUMEN
Schistosomiasis is a parasitic flatworm disease that infects over 200 million people worldwide, especially in poor communities. Treatment and control of the disease rely on just one drug, praziquantel. Since funding for drug development for poverty-associated diseases is very limited, drug repurposing is a promising strategy. In this study, from a screening of 13 marketed diuretics, we identified that spironolactone, a potassium-sparing diuretic, had potent antischistosomal effects on Schistosoma mansoniin vitro and in vivo in a murine model of schistosomiasis. In vitro, spironolactone at low concentrations (<10 µM) is able to alter worm motor activity and the morphology of adult schistosomes, leading to parasitic death. In vivo, oral treatment with spironolactone at a single dose (400 mg/kg) or daily for five consecutive days (100 mg/kg/day) in mice harboring either patent or prepatent infections significantly reduced worm burden, egg production, and hepato- and splenomegaly (P < 0.05 to P < 0.001). Taken together, with the safety profile of spironolactone, supported by its potential to affect schistosomes, these results indicate that spironolactone could be a potential treatment for schistosomiasis and make it promising for repurposing.
Asunto(s)
Reposicionamiento de Medicamentos/métodos , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis/tratamiento farmacológico , Esquistosomicidas/farmacología , Espironolactona/farmacología , Animales , Modelos Animales de Enfermedad , Diuréticos/farmacología , Femenino , Masculino , Ratones , Praziquantel/farmacologíaRESUMEN
The treatment and control of schistosomiasis, a neglected disease that affects more than 200 million people worldwide, rely on the use of a single drug, praziquantel. A vaccine has yet to be developed and since new drug design and development is a lengthy and costly process, drug repurposing is a promising strategy. In this study, the efficacy of promethazine, a first-generation antihistamine, was evaluated against Schistosoma mansoni ex vivo and in a murine model of schistosomiasis. In vitro assays demonstrated that promethazine affected parasite motility, viability, and it induced severe tegumental damage in schistosomes. The LC50 of the drug was 5.84 µM. Similar to promethazine, schistosomes incubated with atropine, a classical anticholinergic drug, displayed reduced motor activity. In an animal model, promethazine treatment was introduced at an oral dose of 100 mg/kg for five successive days at different intervals from the time of infection, for the evaluation of the stage-specific susceptibility (pre-patent and patent infections). Various parasitological criteria indicated the in vivo antischistosomal effects of promethazine: there were significant reductions in worm burden, egg production, and hepato- and splenomegaly. The highest worm burden reduction was achieved with promethazine in patent infections (> 90%). Taken together, considering the importance of the repositioning of drugs in infectious diseases, especially those related to poverty, our data revealed the possibility of promethazine repositioning as an antischistosomal agent.
RESUMEN
In this study, we evaluated the inâ vitro and inâ vivo schistosomicidal activities of chalcones against Schistosoma mansoni worms. In vitro assays revealed that chalcones 1 and 3 were the most active compounds, without affecting significantly mammalian cells. Confocal laser scanning microscopy and scanning electron microscopy studies revealed reduction on the numbers of tubercles and morphological alterations in the tegument of S. mansoni worms after inâ vitro incubation with chalcones 1 and 3. In a mouse model of schistosomiasis, the oral treatment (400â mg/kg) with chalcone 1 or 3 significantly caused a total worm burden reduction in mice. Chalcone 1 showed significant inhibition of the S. mansoni ATP diphosphohydrolase activity, which was corroborated by molecular docking studies. The results suggested that chalcones could be explored as lead compounds with antischistosomal properties.
Asunto(s)
Antihelmínticos/química , Chalconas/farmacología , Schistosoma mansoni/efectos de los fármacos , Administración Oral , Animales , Antihelmínticos/síntesis química , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Apirasa/antagonistas & inhibidores , Apirasa/metabolismo , Sitios de Unión , Chalconas/síntesis química , Chalconas/química , Chalconas/uso terapéutico , Modelos Animales de Enfermedad , Proteínas del Helminto/antagonistas & inhibidores , Proteínas del Helminto/metabolismo , Ratones , Microscopía Confocal , Microscopía Electrónica de Rastreo , Simulación del Acoplamiento Molecular , Estructura Terciaria de Proteína , Schistosoma mansoni/enzimología , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/patología , Relación Estructura-ActividadRESUMEN
Pilocarpus microphyllus Stapf ex Wardlew (Rutaceae), popularly known as jaborandi, is a plant native to the northern and northeastern macroregions of Brazil. Several alkaloids from this species have been isolated. There are few reports of antibacterial and anthelmintic activities for these compounds. In this work, we report the antibacterial and anthelmintic activity of five alkaloids found in P. microphyllus leaves, namely, pilosine, epiisopilosine, isopilosine, epiisopiloturine and macaubine. Of these, only anthelmintic activity of one of the compounds has been previously reported. Nuclear magnetic resonance, HPLC and mass spectrometry were combined and used to identify and confirm the structure of the five compounds. As regards the anthelmintic activity, the alkaloids were studied using in vitro assays to evaluate survival time and damaged teguments for Schistosoma mansoni adult worms. We found epiisopilosine to have anthelmintic activity at very low concentrations (3.125 µg mL-1 ); at this concentration, it prevented mating, oviposition, reducing motor activity and altered the tegument of these worms. In contrast, none of the alkaloids showed antibacterial activity. Additionally, alkaloids displayed no cytotoxic effect on vero cells. The potent anthelmintic activity of epiisopilosine indicates the potential of this natural compound as an antiparasitic agent. Copyright © 2017 John Wiley & Sons, Ltd.
Asunto(s)
Alcaloides/química , Antihelmínticos/química , Antibacterianos/química , Imidazoles/química , Pilocarpus/química , Extractos Vegetales/química , Hojas de la Planta/química , 4-Butirolactona/análogos & derivados , Animales , Imidazoles/farmacología , Células VeroRESUMEN
In recent years, a class of oxindole-copper and -zinc complex derivatives have been reported as compounds with efficient proapoptotic activity toward different tumor cells (e.g., neuroblastomas, melanomas, monocytes). Here we assessed the efficacy of synthesized oxindole-copper(II), -zinc(II), and -vanadyl (VO(2+)) complexes against adult Schistosoma mansoni worms. The copper(II) complexes (50% inhibitory concentrations of 30 to 45 µM) demonstrated greater antischistosomal properties than the analogous zinc and vanadyl complexes regarding lethality, reduction of motor activity, and oviposition.
Asunto(s)
Antihelmínticos/química , Antihelmínticos/farmacología , Complejos de Coordinación/farmacología , Schistosoma mansoni/efectos de los fármacos , Animales , Complejos de Coordinación/química , Cobre/química , Zinc/químicaRESUMEN
Schistosomiasis is one of the world's major public health problems, and its treatment is widely dependent on praziquantel (PZQ), the only available drug. Schistosoma mansoni ATP diphosphohydrolases are ecto-enzymes localized on the external tegumental surface of S. mansoni and considered an important target for action of new drugs. In this work, the in vitro schistosomicidal activity of the crude extract of Glycyrrhiza inflata roots (GI) and its isolated compounds echinatin, licoflavone A and licoflavone B were evaluated against S. mansoni adult worms. Results showed that GI (200 µg/mL) was active against adult schistosomes, causing 100% mortality after 24 h of incubation. Chromatographic fractionation of GI led to isolation of echinatin, licoflavone A and licoflavone B. Licoflavone B (25-100 µM) caused 100% mortality, tegumental alterations, and reduction of oviposition and motor activity of all adult worms, without affecting mammalian Vero cells. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms in a dose-dependent manner after incubation with licoflavone B. Licoflavone B also showed high S. mansoni ATPase (IC50 of 23.78 µM) and ADPase (IC50 of 31.50 µM) inhibitory activities. Docking studies predicted different interactions between licoflavone B and S. mansoni ATPDase 1, corroborating with the in vitro inhibitory activity. This report demonstrated the first evidence for the schistosomicidal activity of licoflavone B and suggests that its mechanism of action involve the inhibition of S. mansoni ATP diphosphohydrolases.
Asunto(s)
Apirasa/antagonistas & inhibidores , Flavonas/farmacología , Glycyrrhiza/química , Extractos Vegetales/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomicidas/farmacología , Animales , Biomphalaria , Cricetinae , Femenino , Flavonas/química , Flavonas/aislamiento & purificación , Masculino , Mesocricetus , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Reproducción , Schistosoma mansoni/enzimología , Esquistosomicidas/química , Esquistosomicidas/aislamiento & purificaciónRESUMEN
Schistosomiasis is a neglected tropical disease caused by blood flukes of the genus Schistosoma. This disease control has been widely made by praziquantel-reference drug, but resistance to this drug has already been found. There has been the finding of an imidazole alkaloid in jaborandi leaves-epiisopiloturine, which has known activity against adult, young and egg forms of Schistosoma mansoni. This alkaloid is an apolar molecule with difficult solubility; therefore, the liposomal structure of epiisopiloturine was proposed. Liposomes are carrying structures of drugs that may enhance solubility of compounds such as epiisopiloturine. In this work, we report in vitro epiisopiloturine-loaded liposomes effect formed by different concentrations of lipids 9:1 (weight ratio) dipalmitoylphosphatidylcholine:cholesterol and 8:2 (weight ratio) dipalmitoylphosphatidylcholine:cholesterol. Results have showed that epiisopiloturine extraction and isolation have been successful through high-performance liquid chromatography-HPLC and its purity confirmed through mass spectrometry has showed 287 Da molecular mass. Formulations from 9:1 DPPC:cholesterol and 8:2 DPPC:cholesterol with loaded EPI (300 microg/ml) have killed parasites at 100% after incubation 96 h and 120 h, respectively. Confocal microscopy employed to observe morphological alterations in the tegument of adult form of Schistosoma mansoni. Details from interaction, between epiisopiloturine and liposome, have been achieved by semi-empirical AM1 calculations, which have showed that epiisopiloturine inside is more stable than the outside form, at least 10 kcal. This is first time that schistosomicidal activity has been reported for epiisopiloturine-loaded into liposome.
Asunto(s)
4-Butirolactona/análogos & derivados , Imidazoles/síntesis química , Imidazoles/farmacología , Liposomas/química , Nanocápsulas/administración & dosificación , Schistosoma mansoni/efectos de los fármacos , Schistosoma mansoni/fisiología , 4-Butirolactona/síntesis química , 4-Butirolactona/farmacología , Animales , Antihelmínticos/síntesis química , Antihelmínticos/farmacología , Ensayo de Materiales , Nanocápsulas/química , Schistosoma mansoni/anatomía & histología , Resultado del TratamientoRESUMEN
Schistosomiasis, a parasitic disease caused by trematode flatworms of the genus Schistosoma, affects more than 200 million people worldwide, and its control is dependent on a single drug, praziquantel. Tanacetum vulgare (Asteraceae) is used in folk medicine as a vermifuge. This study aimed to investigate the in vitro schistosomicidal activity of the crude extract (TV) and the essential oil (TV-EO) from the aerial parts of T. vulgare. TV-EO was obtained by hydrodistillation and analyzed by GC/MS, which allowed the identification of ß-thujone (84.13%) as the major constituent. TV and TV-EO, at 200 µg/mL, decreased motor activity and caused 100% mortality of all adult worms. At 100 and 50 µg/mL, only TV caused death of all adult worms, while TV-EO was inactive. TV (200 µg/mL) was also able to reduce viability and decrease production of developed eggs. Confocal laser scanning microscopy showed morphological alterations in the tegument of the S. mansoni surface after incubation with TV (50 and 100 µg/mL). Quantitative analysis on the schistosomes tegument showed that TV caused changes in the numbers of tubercles of S. mansoni male worms in a dose-dependent manner. The findings suggest that T. vulgare is a potential source of schistosomicidal compounds.
Asunto(s)
Antihelmínticos/farmacología , Extractos Vegetales/farmacología , Schistosoma mansoni/efectos de los fármacos , Tanacetum/química , Animales , Microscopía ConfocalRESUMEN
Schistosomiasis is a neglected tropical disease that affects hundreds of millions of people worldwide. Since the treatment of this disease currently relies on a single drug, praziquantel, new and safe schistosomicidal agents are urgently required. Nerolidol, a sesquiterpene present in the essential oils of several plants, is found in many foods and was approved by the U.S. Food and Drug Administration. In this study we analysed the in vitro antiparasitic effect of nerolidol on Schistosoma mansoni adult worms. Nerolidol at concentrations of 31.2 and 62.5 µM reduced the worm motor activity and caused the death of all male and female schistosomes, respectively. In addition, confocal laser scanning microscopy revealed morphological alterations on the tegument of worms such as disintegration, sloughing and erosion of the surface, and a correlation between viability and tegumental damage was observed. In conclusion, nerolidol may be a promising lead compound for the development of antischistosomal natural agents.