RESUMEN
Two novel compounds bearing heterocyclic nitrogen, 2-pyridone alkaloid (1) and alloxazine derivative (2), along with the known pretenellin B (3), pyridovericin (4) and lumichrome (5) were isolated from a culture of the entomopathogenic fungal strain Beauveria bassiana. The chemical structures of 2-pyridone alkaloid and alloxazine derivative were established on the basis of the interpretation of spectroscopic data. The isolated compounds were evaluated in a panel of five cancer cell lines and pyridovericin exhibited cytotoxicity (IC50, µM) against cancer cell lines: HL-60 (25.9 ± 0.3), HCT8 (34.6 ± 3.6), MDA-MB435 (34.8 ± 3.8) and SF295 (31.1 ± 0.6). Considering that other pyridone compounds display good cytotoxic activity, it would be suggested to obtain new semi synthetic derivatives of pyridovericin, for the development of new cytotoxic chemical entities.
Asunto(s)
Alcaloides/química , Antineoplásicos/farmacología , Beauveria/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Antineoplásicos/química , Beauveria/metabolismo , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Flavinas/química , Flavinas/aislamiento & purificación , Humanos , Estructura Molecular , Monosacáridos/química , Piridonas/química , Piridonas/aislamiento & purificación , Piridonas/farmacología , Metabolismo SecundarioRESUMEN
Eugenitin, a chromone derivative and a metabolite of the endophyte Mycoleptodiscus indicus, at 5 mM activated a recombinant GH11 endo-xylanase by 40 %. The in silico prediction of ligand-binding sites on the three-dimensional structure of the endo-xylanase revealed that eugenitin interacts mainly by a hydrogen bond with a serine residue and a stacking interaction of the heterocyclic aromatic ring system with a tryptophan residue. Eugenitin improved the GH11 endo-xylanase activity on different substrates, modified the optimal pH and temperature activities and slightly affected the kinetic parameters of the enzyme.
Asunto(s)
Ascomicetos/química , Cromonas/farmacología , Endo-1,4-beta Xilanasas/metabolismo , Aspergillus/enzimología , Aspergillus/genética , Aspergillus/metabolismo , Cromonas/química , Cromonas/metabolismo , Dimetilsulfóxido , Endo-1,4-beta Xilanasas/química , Endófitos/química , Activación Enzimática , Estabilidad de Enzimas , Concentración de Iones de Hidrógeno , Hidrólisis , Cinética , Modelos Moleculares , Programas Informáticos , TemperaturaRESUMEN
(±)-Licarin A (1) was obtained by oxidative coupling, and its enantiomers, (-)-licarin A (2) and (+)-licarin A (3), were resolved by chiral HPLC. Schistosomicidal and trypanocidal activities of these compounds were evaluated in vitro against Schistosoma mansoni adult worms and trypomastigote forms of Trypanosoma cruzi. The racemic mixture (1) displayed significant schistosomicidal activity with an LC50 value of 53.57 µM and moderate trypanocidal activity with an IC50 value of 127.17 µM. On the other hand, the (-)-enantiomer (2), displaying a LC50 value of 91.71 µM, was more active against S. mansoni than the (+)-enantiomer (3), which did not show activity. For the trypanocidal assay, enantiomer 2 showed more significant activity (IC50 of 23.46 µM) than enantiomer 3, which showed an IC50 value of 87.73 µM. Therefore, these results suggest that (±)-licarin A (1) and (-)-licarin A (2) are promising compounds that could be used for the development of schistosomicidal and trypanocidal agents.
Asunto(s)
Lignanos/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomicidas/química , Tripanocidas/química , Trypanosoma cruzi/efectos de los fármacos , Animales , Chlorocebus aethiops , Cromatografía Líquida de Alta Presión/métodos , Femenino , Concentración 50 Inhibidora , Lignanos/química , Masculino , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Acoplamiento Oxidativo , Esquistosomicidas/farmacología , Relación Estructura-Actividad , Tripanocidas/farmacología , Células VeroRESUMEN
Baccharis dracunculifolia DC. (Asteraceae), popularly known as 'alecrim do campo', is a native plant from Brazil used in folk medicine as febrifuge, anti-inflammatory, antiseptic, and to treat skin sores. Also, B. dracunculifolia is the most important plant source of the Brazilian green propolis, which is recognized for its antiseptic and antiprotozoal activities. This study aimed at investigating the in vitro antiprotozoal, schistosomicidal, and antimicrobial activities of the essential oil from the leaves of B. dracunculifolia. The essential oil was obtained by hydrodistillation and analyzed by GC and GC/MS, which allowed the identification of 14 compounds, mainly oxygenated sesquiterpenes, such as (E)-nerolidol (33.51%) and spathulenol (16.24%). The essential oil showed activity against promastigote forms of Leishmania donovani, with IC(50) values of 42 microg/ml. The essential oil displayed high activity in the schistosomicidal assay, since all pairs of Schistosoma mansoni adult worms were dead after incubation with the essential oil (10, 50, and 100 microg/ml). B. dracunculifolia essential oil was neither cytotoxic against Vero cells, nor active in the antimicrobial and antiplasmodial assays.
Asunto(s)
Antiinfecciosos/química , Antiprotozoarios/química , Asteraceae/química , Aceites Volátiles/química , Aceites de Plantas/química , Esquistosomicidas/química , Antiinfecciosos/farmacología , Antiprotozoarios/farmacología , Aceites Volátiles/farmacología , Hojas de la Planta/química , Aceites de Plantas/farmacología , Esquistosomicidas/farmacologíaRESUMEN
Baccharis dracunculifolia (Asteraceae), the most important plant source of the Brazilian green propolis (GPE), displayed in vitro activity against Leishmania donovani, with an IC(50) value of 45 microg/mL, while GPE presented an IC(50) value of 49 microg/mL. Among the isolated compounds of B. dracunculifolia, ursolic acid, and hautriwaic acid lactone showed IC(50) values of 3.7 microg/mL and 7.0 microg/mL, respectively. Uvaol, acacetin, and ermanin displayed moderate antileishmanial activity. Regarding the antiplasmodial assay against Plasmodium falciparum, BdE and GPE gave similar IC(50) values (about 20 microg/mL), while Hautriwaic acid lactone led to an IC(50) value of 0.8 microg/mL (D6 clone).
Asunto(s)
Antimaláricos/farmacología , Baccharis/química , Fenoles/farmacología , Extractos Vegetales/farmacología , Triterpenos/farmacología , Tripanocidas/farmacología , Animales , Antimaláricos/efectos adversos , Antimaláricos/aislamiento & purificación , Chlorocebus aethiops , Leishmania donovani/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Pruebas de Sensibilidad Parasitaria , Fenoles/efectos adversos , Fenoles/aislamiento & purificación , Extractos Vegetales/efectos adversos , Extractos Vegetales/química , Hojas de la Planta , Plasmodium falciparum/efectos de los fármacos , Própolis , Triterpenos/efectos adversos , Triterpenos/aislamiento & purificación , Tripanocidas/efectos adversos , Tripanocidas/aislamiento & purificación , Células VeroRESUMEN
BACKGROUND: We hypothesized that the alkaloid compounds that are the majority components of fire ant (Solenopsis invicta) venom are capable of producing cardiovascular and central nervous system toxic effects in mammals. OBJECTIVE: To evaluate toxic effects of synthetic S. invicta alkaloids in rodent models. METHODS: Cardiovascular effects of intravenous injection of the racemic (+/-)-cis- and trans-isomers of 2-methyl-6-nundecylpiperidine (isosolenopsin A and solenopsin A, respectively) were evaluated in anesthetized, gallamine-paralyzed rats who had received artificial ventilation and in isolated, perfused rat hearts. RESULTS: (+/-)-Solenopsin A dose dependently (3-30 mg/kg [10 to 104 micromol/kg]) depressed cardiovascular function. Maximal percent changes following injection of 30 mg/kg were -42.96% +/- 5.8% for blood pressure, -29.13% +/- 3.6% for heart rate, and -43.5% +/- 9.2% for left ventricular contractility (dP/dt). (+/-)-Isosolenopsin A (3-15 mg/kg [10 to 52 micromol/kg]) produced responses similar to those seen with the corresponding doses of solenopsin A. In conscious, spontaneously breathing rats, solenopsin A (30 mg/kg intravenously) caused seizures, respiratory arrest, and death. Infusion of working, isolated, perfused hearts with solenopsin A reduced contractile function (dP/dt) at 10 microM and caused cardiac arrest at 100 microM. CONCLUSIONS: Two alkaloid components of imported fire ant venom possess robust cardiorespiratory depressant activity and elicit seizures in the rat. Such effects identify these alkaloids as toxic compounds in biological systems and may explain the cardiorespiratory failure noted in some individuals who experience massive fire ant stings.
Asunto(s)
Alcaloides/farmacología , Venenos de Hormiga/farmacología , Sistema Nervioso Central/efectos de los fármacos , Corazón/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Animales , Femenino , Paro Cardíaco/inducido químicamente , Técnicas In Vitro , Masculino , Modelos Animales , Ratas , Ratas Sprague-Dawley , Convulsiones/inducido químicamenteRESUMEN
The roots of Caulophyllum thalictroides, traditionally used for the treatment of menstrual difficulties and as an aid in childbirth, contain saponins, which are considered to be responsible for the uterine stimulant effects, together with teratogenic alkaloids. An HPLC method has been developed which permits the determination of the triterpene saponins in the plant and also the separation of four alkaloids. The best results were obtained with a C-12 stationary phase using ammonium acetate buffer (pH 8.0) and acetonitrile as mobile phase. Owing to their low UV absorbance, the saponins were detected by evaporative light scattering, whereas the alkaloids were monitored by UV at 310 nm. The identities of the compounds were confirmed in an LC-MS experiment. Different plant samples and commercial products have been analysed using the described method, and remarkable qualitative and quantitative variations were revealed. Comparing the daily uptake of total saponins, a difference of greater than 100-fold was observed within the various products; the alkaloid content on the other hand was more uniform.