RESUMEN
Licarin A, a dihydrobenzofuranic neolignan presents in several medicinal plants and seeds of nutmeg, exhibits strong activity against protozoans responsible for Chagas disease and leishmaniasis. From biomimetic reactions by metalloporphyrin and Jacobsen catalysts, seven products were determined: four isomeric products yielded by epoxidation from licarin A, besides a new product yielded by a vicinal diol, a benzylic aldehyde, and an unsaturated aldehyde in the structure of the licarin A. The incubation with rat and human liver microsomes partially reproduced the biomimetic reactions by the production of the same epoxidized product of m/z 343 [M + H]+. In vivo acute toxicity assays of licarin A suggested liver toxicity based on biomarker enzymatic changes. However, microscopic analysis of tissues sections did not show any tissue damage as indicative of toxicity after 14 days of exposure. New metabolic pathways of the licarin A were identified after in vitro biomimetic oxidation reaction and in vitro metabolism by rat or human liver microsomes.
Asunto(s)
Lignanos , Metaloporfirinas , Ratas , Humanos , Animales , Biomimética , Oxidación-Reducción , Lignanos/toxicidad , Metaloporfirinas/metabolismo , Microsomas Hepáticos/metabolismoRESUMEN
Chagas disease is a neglected protozoan disease that affects more than eight million people in developing countries. Due to the limited number and toxicity profiles of therapies in current use, new drugs are urgently needed. In previous studies, we reported the isolation of two related antitrypanosomal neolignans from Nectandra leucantha (Lauraceae). In this work, a semi-synthetic library of twenty-three neolignan derivatives was prepared to explore synthetically accessible structure activity relationships (SAR) against Trypanosoma cruzi. Five compounds demonstrated activity against trypomastigotes (IC50 values from 8 to 64⯵M) and eight showed activity against intracellular amastigotes (IC50 values from 7 to 16⯵M). Eighteen derivatives demonstrated no mammalian cytotoxicity up to 200⯵M. The phenolic acetate derivative of natural dehydrodieugenol B was effective against both parasite forms and eliminated 100% of amastigotes inside macrophages. This compound caused rapid and intense depolarization of the mitochondrial membrane potential, with decreased levels of intracellular reactive oxygen species being observed. Fluorescence assays demonstrated that this derivative affected neither the permeability nor the electric potential of the parasitic plasma membrane, an effect also corroborated by scanning electron microscopy studies. Structure-activity relationship studies (SARs) demonstrated that the presence of at least one allyl side chain on the biaryl ether core was important for antitrypanosomal activity, and that the free phenol is not essential. This set of neolignan derivatives represents a promising starting point for future Chagas disease drug discovery studies.
Asunto(s)
Anisoles/farmacología , Lignanos/farmacología , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Anisoles/síntesis química , Anisoles/química , Anisoles/toxicidad , Línea Celular , Membrana Celular/efectos de los fármacos , Humanos , Lignanos/síntesis química , Lignanos/química , Lignanos/toxicidad , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos BALB C , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad , Tripanocidas/síntesis química , Tripanocidas/química , Tripanocidas/toxicidad , Trypanosoma cruzi/crecimiento & desarrollo , Trypanosoma cruzi/metabolismoRESUMEN
Aiouea trinervis Meisn. is a shrub that grows in the "Cerrado" (a savanna ecosystem) of Brazil. In this study, fractionation of ethanol extracts (EEs) from the leaves of A. trinervis led to the isolation of butanolides, namely isoobtusilactone A and obtusilactone A, as well as lignans, namely sesamin, methylpiperitol, and polyprenol-12. Their structures were determined by spectroscopic analyses. The genotoxic properties were evaluated for mutagenic and recombinogenic effects using the wing spot test (somatic mutation and recombination test, SMART) on Drosophila melanogaster. The standard and high bioactivation crosses were used. The latter cross is characterized by high sensitivity to promutagens and procarcinogens. EEs were evaluated at concentrations of 0.625, 1.25, and 2.5 mg/mL. Butanolides (isoobtusilactone A and obtusilactone A) were evaluated at concentrations of 0.1, 0.2, and 0.3 mg/mL. The results observed in both crosses were similar and indicated that EEs from the leaves of A. trinervis did not show genotoxicity at the doses that were used. However, the individuals resulting from standard and high bioactivation crosses that were treated with isoobtusilactone A and obtusilactone A showed statistically significant increases in mutant spots compared to those that were obtained in the negative control. Similar results were obtained between standard and high bioactivation crosses, indicating that butanolides had a genotoxic activity.
Asunto(s)
Drosophila melanogaster/efectos de los fármacos , Lauraceae/química , Lignanos/toxicidad , Pruebas de Mutagenicidad , Mutágenos/toxicidad , Extractos Vegetales/toxicidad , Alcanos/toxicidad , Animales , Drosophila melanogaster/genética , Lactonas/toxicidad , Extractos Vegetales/química , Hojas de la Planta/metabolismo , Recombinación Genética , Metabolismo SecundarioRESUMEN
Leishmaniasis' treatment is based mostly on pentavalent antimonials or amphotericin B long-term administration, expensive drugs associated with severe side effects. Considering these aforementioned, the search for alternative effective and safe leishmaniasis treatments is a necessity. This work evaluated a neolignan, licarin A anti-leishmanial activity chemically synthesized by our study group. It was observed that licarin A effectively inhibited Leishmania (Leishmania) major promastigotes (IC50 of 9.59 ± 0.94 µg/mL) growth, by inducing in these parasites genomic DNA fragmentation in a typical death pattern by apoptosis. Additionally, the neolignan proved to be even more active against intracellular amastigotes of the parasite (EC50 of 4.71 ± 0.29 µg/mL), and significantly more effective than meglumine antimoniate (EC50 of 216.2 ± 76.7 µg/mL) used as reference drug. The antiamastigote activity is associated with an immunomodulatory activity, since treatment with licarin A of the infected macrophages induced a decrease in the interleukin (IL)-6 and IL-10 production. This study demonstrates for the first time the antileishmanial activity of licarin A and suggests that the compound may be a promising in the development of a new leishmanicidal agent.
Asunto(s)
Antiprotozoarios/farmacología , Factores Inmunológicos/farmacología , Leishmania major/efectos de los fármacos , Leishmaniasis Cutánea/tratamiento farmacológico , Lignanos/farmacología , Anfotericina B/farmacología , Animales , Antiprotozoarios/toxicidad , Apoptosis , Citocinas/metabolismo , Fragmentación del ADN , Femenino , Factores Inmunológicos/toxicidad , Concentración 50 Inhibidora , Leishmania major/genética , Lignanos/toxicidad , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/parasitología , Meglumina/farmacología , Meglumina/toxicidad , Antimoniato de Meglumina , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico/metabolismo , Compuestos Organometálicos/farmacología , Compuestos Organometálicos/toxicidadRESUMEN
The hydroalcoholic extract of the steam bark of B. fagaroides var. fagaroides displayed potent cytotoxic activity against four cancer cell lines, namely KB (ED50 = 9.6 × 10(-2) µg/mL), PC-3 (ED50 = 2.5 × 10(-1) µg/mL), MCF-7 (ED50 = 6.6 µg/mL), and HF-6 (ED50 = 7.1 × 10(-3) µg/mL). This extract also showed anti-tumour activity when assayed on mice inoculated with L5178Y lymphoma cells. Bioactivity-directed isolation of this extract, afforded seven podophyllotoxin-type lignans identified as podophyllotoxin (1), ß-peltatin-A-methylether (2), 5'-desmethoxy-ß-peltatin-A-methylether (3), desmethoxy-yatein (4), desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7) by 1D and 2DNMR and FAB-MS analyses, and comparison with reported values. All the isolated compounds showed potent cytotoxic activity in the cell lines tested, especially compound 3, which exhibited greater activity than camptothecin and podophyllotoxin against PC-3 (ED50= 1.0 × 10(-5) µg/mL), and KB (ED50 = 1.0 × 10(-5) µg/mL). This is the first report of the isolation of podophyllotoxin and its acetate in a Bursera species.
Asunto(s)
Antineoplásicos Fitogénicos/toxicidad , Bursera/química , Lignanos/toxicidad , Podofilotoxina/toxicidad , Animales , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Humanos , Lignanos/administración & dosificación , Lignanos/química , Lignanos/aislamiento & purificación , Linfoma/tratamiento farmacológico , Linfoma/mortalidad , Masculino , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Podofilotoxina/administración & dosificación , Podofilotoxina/aislamiento & purificación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
CONTEXT: Neolignans are usually dimers formed by oxidative coupling of allyl and propenyl phenols, and the neolignan analogue, 2-phenoxy-1-phenylethanone (LS-2) is a promising antimycobacterial compound showing very weak cytotoxicity in mammalian cells and lack of acute toxicity in murine models. OBJECTIVES: To investigate the mechanism of action of LS-2 in rat hepatocytes by evaluating the activity levels of enzymes related to oxidation status and drug-metabolizing activity. MATERIALS AND METHODS: Hepatocytes were treated with LS-2 from 0.05 up to 1 mM, for 24 and 48 h, and reduced glutathione (GSH), lipid peroxidation and cytochrome P450 enzyme (CYP450) activity were assayed. A homologous series of phenoxazone ethers were used as substrates to measure the enzymatic profile. The biotransformation of LS-2 was studied in hepatocytes by gas chromatography-mass spectrometry (GC-MS) for detection and analysis of possible metabolites. RESULTS: Hepatocytes treated with LS-2 up to 1 mM for 24 or 48 h did not induce the formation of GSH and lipid peroxidation. O-Dealkylation activities of the isoenzymes CYP4501A1, CYP4501A2, CYP4502B1 and CYP4502B2 were also not detected in the hepatocytes treated with LS-2 for 24 or 48 h. DISCUSSION AND CONCLUSION: The results indicate that LS-2 or its two detected metabolites, 2-phenoxy-1-phenylethanol and 2,4-(2-hydroxy-2-phenylethoxy)phenol, are not cytotoxic to rat hepatocytes. These compounds maintain a balance between the production of pro-oxidant agents and their respective antioxidant systems. The data show that enzymes related to oxidation status and drug-metabolizing activities are not involved in the mechanism of action of LS-2.
Asunto(s)
Antibacterianos/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo , Hepatocitos/efectos de los fármacos , Lignanos/farmacología , Animales , Antibacterianos/metabolismo , Antibacterianos/toxicidad , Antioxidantes/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Glutatión/metabolismo , Hepatocitos/metabolismo , Lignanos/metabolismo , Lignanos/toxicidad , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
(-)-Cubebin belongs to the dibenzylbutyrolactone lignan group, which is widely distributed in the plant kingdom. Because this compound shows interesting biological activities, it is extremely important to evaluate its possible genotoxic activity to allow its safe use in humans. Thus, the present study was performed to investigate the genotoxicity potential activity of (-)-cubebin assessed by two assays: micronucleus in bone marrow cells and comet test in peripheral blood leukocytes of Swiss mice. In the (-)-cubebin dose range-finding assays, the maximum tolerated dose was greater than 2000 mg kg(-1) . The compound was administered by an oral route at single doses of 250, 500 and 2000 mg kg(-1) body weight. Cytotoxicity was assessed by scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). Under our experimental conditions, micronucleus and comet assays, respectively, showed that (-)-cubebin caused dose-related clastogenic and genotoxic effects in the somatic cells investigated. PCE/NCE ratio showed no cytotoxicity for the three doses of the compound. The data suggest caution in the ingestion of (-)-cubebin by humans, especially at high doses.
Asunto(s)
Antiinflamatorios no Esteroideos/toxicidad , Células de la Médula Ósea/efectos de los fármacos , Daño del ADN , Leucocitos/efectos de los fármacos , Lignanos/toxicidad , Mutágenos/toxicidad , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/aislamiento & purificación , Ensayo Cometa , Relación Dosis-Respuesta a Droga , Lignanos/administración & dosificación , Lignanos/aislamiento & purificación , Masculino , Ratones , Pruebas de Micronúcleos , Mutágenos/administración & dosificación , Mutágenos/aislamiento & purificación , Piper/química , Semillas/químicaRESUMEN
Preclinical investigations can start with preliminary in vitro studies before using animal models. Following this approach, the number of animals used in preclinical acute toxicity testing can be reduced. In this study, we employed an in-house validated in vitro cytotoxicity test based on the Spielmann approach for toxicity evaluation of the lignan grandisin, a candidate anticancer agent, and its major metabolite, the 4-O-demethylgrandisin, by neutral red uptake (NRU) assay, on mouse fibroblasts Balb/c 3T3 cell line. Using different concentrations of grandisin and its major metabolite (2.31; 1.16; 0.58; 0.29; 0.14; 0.07; 0.04; 0.002 µM) in Balb/c 3T3-A31 NRU cytotoxicity assay, after incubation for 48 h, we obtained IC(50) values for grandisin and its metabolite of 0.078 and 0.043 µM, respectively. The computed LD(50) of grandisin and 4-O-demethylgrandisin were 617.72 and 429.95 mg/kg, respectively. Both were classified under the Globally Harmonized System as category 4. Since pharmacological and toxicological data are crucial in the developmental stages of drug discovery, using an in vitro assay we demonstrated that grandisin and its metabolite exhibit distinct toxicity profiles. Furthermore, results presented in this work can contribute to reduce the number of animals required in subsequent pharmacological/toxicological studies.
Asunto(s)
Alternativas a las Pruebas en Animales/métodos , Furanos/toxicidad , Lignanos/toxicidad , Pruebas de Toxicidad Aguda/métodos , Animales , Células 3T3 BALB , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Furanos/química , Furanos/aislamiento & purificación , Furanos/metabolismo , Lignanos/química , Lignanos/aislamiento & purificación , Lignanos/metabolismo , Ratones , Estructura Molecular , Piper/química , Extractos Vegetales/química , Hojas de la Planta/químicaRESUMEN
The dibenzylbutyrolactone lignan (-)-hinokinin (HK) was obtained by partial synthesis from (-)-cubebin, isolated from the dry seeds of the pepper, Piper cubeba. In view of the trypanocidal activity of HK and its potential as a lead compound for drug development, evaluation of its possible genotoxic activity is required. We have tested HK for possible genotoxicity and evaluated the compound's effect on the activity of the clastogens doxorubicin (DXR) and methyl methanesulfonate (MMS) in the micronucleus (MN) assay with Chinese hamster lung fibroblast V79 cells. HK alone did not induce MN, at concentrations up to 128microM. In combined treatments, HK reduced the frequency of MN induced by MMS. With respect to DXR, HK exerted a protective effect at lower concentrations, but at higher concentrations it potentiated DXR clastogenicity.
Asunto(s)
4-Butirolactona/análogos & derivados , Dioxoles/toxicidad , Doxorrubicina/toxicidad , Lignanos/toxicidad , Metilmetanosulfonato/toxicidad , Mutágenos/toxicidad , 4-Butirolactona/farmacología , 4-Butirolactona/toxicidad , Animales , Benzodioxoles , Línea Celular , Cricetinae , Cricetulus , Dioxoles/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Fibroblastos/efectos de los fármacos , Lignanos/farmacología , Pulmón/efectos de los fármacos , Pruebas de MicronúcleosRESUMEN
Trypanosoma cruzi is the ethiological agent for Chagas disease in Latin America. This study aimed to test the trypanocidal effect of licarin A and burchellin isolated from plants in northeastern Brazil. These neolignans were tested on T. cruzi and on peritoneal macrophages, to evaluate drug toxicity. Epimastigote growth was inhibited in 45% with licarin A and 20% with burchellin with an IC(50)/96 h of 462.7 microM and 756 microM, respectively. Epimastigotes treated with licarin A presented swollen mitochondria and disorganized mitochondrial cristae, kDNA and Golgi complex. When treated with burchellin, they presented enormous autophagosomes and chromatin disorganization. Licarin A and burchellin were able to induce trypomastigote death with IC(50)/24 h of 960 microM and 520 microM, respectively. Although licarin A presented an IC(50) for trypomastigotes higher than for epimastigotes, both substances acted as therapeutic trypanocidal agents, because they were able to kill parasites without affecting macrophages. Due to our results, burchellin and licarin A need to be further analysed to observe if they may be used as alternative blood additive prophylaxis against Chagas disease, since it has been established that blood transfusion is an important mechanism in the transmission process.
Asunto(s)
Benzofuranos/farmacología , Lignanos/farmacología , Macrófagos Peritoneales/efectos de los fármacos , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Benzofuranos/química , Benzofuranos/toxicidad , Transfusión Sanguínea/normas , Brasil , Supervivencia Celular/efectos de los fármacos , Enfermedad de Chagas/prevención & control , Enfermedad de Chagas/transmisión , Humanos , Concentración 50 Inhibidora , Lignanos/química , Lignanos/toxicidad , Macrófagos Peritoneales/citología , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Transmisión , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Tripanocidas/química , Tripanocidas/toxicidad , Trypanosoma cruzi/crecimiento & desarrollo , Trypanosoma cruzi/ultraestructuraRESUMEN
The in vitro cytotoxic potential of yangambin was evaluated. Yangambin is a pharmacologically active furofuran lignan obtained from the leaves of Ocotea duckei. It is the major compound from the lignoids fraction. Yangambin presented low cytotoxicity in all in vitro models analyzed. Its cytotoxicity to murine macrophages was measured by the Trypan blue dye exclusion test and MTT reduction assay, resulting in high CC50 values of 187.0 microg/mL (383.3 microM) and 246.7 microg/mL (504.3 microM), respectively. The difference obtained in the inhibitory concentrations aforementioned can be explained, at least in part, by the different principles of the methods. While the MTT reduction assay evaluates the ability of yangambin to inhibit the activity of the mitochondrial enzyme succinate dehydrogenase, the Trypan blue dye exclusion test evaluates possible damages to the integrity of the cytoplasmic membrane which result in cell death. The capacity of yangambin to inhibit the sea urchin embryonic development showed that it has low antimitotic and teratogenic potential, once continued exposure of embryos to concentrations up to 500 microg/mL (1.025 microM) did not result in an inhibitory effect on the first egg cleavages. Such low in vitro cytotoxicity is correlated with the low acute toxicity previously studied. All these data, together with the various therapeutic properties of yangambin, make this lignan a promising one for a new drug.
Asunto(s)
Furanos/toxicidad , Lignanos/toxicidad , Macrófagos Peritoneales/efectos de los fármacos , Ocotea/química , Extractos Vegetales/toxicidad , Animales , Supervivencia Celular/efectos de los fármacos , Embrión no Mamífero/efectos de los fármacos , Etanol , Furanos/aislamiento & purificación , Lignanos/aislamiento & purificación , Macrófagos Peritoneales/citología , Ratones , Modelos Moleculares , Extractos Vegetales/química , Hojas de la Planta/química , Erizos de Mar/efectos de los fármacos , Erizos de Mar/embriologíaRESUMEN
The in vitro evaluation of a series of 8.O.4'-neolignans (in their ketone, alcohol, and acetylated forms) on the proliferation of Trypanosoma cruzi led to the detection of three compounds with interesting activities against T. cruzi epimastigotes. These compounds also inhibited the in vitro differentiation of epimastigotes to trypomastigotes. When tested against HeLa cells, the same compounds did not affect the cell vitality and showed a low influence on cell viability as measured by dimethylthiazol diphenyltetrazolium bromide reduction. The three phenylpropanoid moieties tested did not show any activity against T. cruzi. One of the tested compounds, compound 4 (3,4-methylenedioxi7-oxo-1'-allyl-3',5'-dimethoxy-8.O.4'-neolignan) showed the best performance in both trypanocide and cytotoxic assays, suggesting that it should be considered as a leading structure for further research.
Asunto(s)
Antiprotozoarios/farmacología , Lignanos/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Supervivencia Celular , Células HeLa/efectos de los fármacos , Humanos , Lignanos/toxicidad , Trypanosoma cruzi/crecimiento & desarrolloRESUMEN
Phytochemicals endowed with hormonal, antihormonal, or toxic activity are potential agents for insect control. Thus, we became interested in testing Brazilian plant metabolites on Chrysomya megacephala (F.) (Diptera: Calliphoridae), a public health menace that is one of the most prevalent flies in Brazilian urban areas. We tested the lignan yangambin, from the leaves of Ocotea duckei Vattimo (Lauraceae). Topical treatment of eggs and first instars with yangambin as well as feeding larvae a yangambin-treated diet resulted in inhibition of postembryonic development, morphological alteration, and oviposition reduction.
Asunto(s)
Dípteros/efectos de los fármacos , Furanos/toxicidad , Lignanos/toxicidad , Ocotea/química , Extractos Vegetales/toxicidad , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Dípteros/crecimiento & desarrollo , Femenino , Furanos/administración & dosificación , Furanos/química , Control de Insectos/métodos , Larva/efectos de los fármacos , Lignanos/administración & dosificación , Lignanos/química , Masculino , Óvulo/efectos de los fármacos , Razón de Masculinidad , Factores de TiempoRESUMEN
Phytochemicals endowed with hormonal, antihormonal, or toxic activity are potential agents for insect control. The effect of some neolignans on one of the most prevalent flies in urban areas, which constitutes a menace to public health, was investigated.
Asunto(s)
Dípteros/efectos de los fármacos , Insecticidas/toxicidad , Lauraceae , Lignanos/toxicidad , Fitoterapia , Piperaceae , Extractos Vegetales/toxicidad , Animales , Dípteros/crecimiento & desarrollo , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Control Biológico de VectoresRESUMEN
The effects of phytochemicals (lignans and neolignans) are reviewed in a variety of insect species with special focus on the recent advances on feeding, excretion and Trypanosoma cruzi interactions with Rhodnius prolixus. Burchellin, podophyllotoxin, pinoresinol, sesamin, licarin A, and nordihydroguaiaretic acid (NDGA) added to the diet of Rhodnius prolixus larvae induce antifeedant effects only in doses up to 100 microg/ml of blood meal. Additionally, pinoresinol and NDGA significantly inhibit ecdysis (ED(50)<20 microg/ml). Simultaneous application of ecdysone (1 microg/ml) counteracts ecdysial stasis as induced by NDGA in 5th-instar larvae. Experiments in vivo demonstrate that burchellin and podophyllotoxin (100 microg/ml) diminish excretion post-feeding. Simultaneous treatment with 5-hydroxytryptamine (1 mM, 5-HT), a diuretic hormone, partially reverses this effect of burchellin. Experiments in vitro, using isolated Malpighian tubules of R. prolixus, indicate that burchellin (i) decreases diuretic hormone levels in the hemolymph but not the amount of diuretic hormone stored in the thoracic ganglionic masses (including axons); (ii) reduces the volume of urine secreted by isolated Malpighian tubules; and (iii) 5-HT therapy cannot overcome the effect of burchellin on the Malpighian tubules. In R. prolixus fed on blood containing T. cruzi epimastigotes, the number of parasites in the digestive tract decreases drastically in the presence of burchellin and NDGA (10 microg/ml). When these phytochemicals are applied 20 days after T. cruzi infection, burchellin significantly reduces the gut infection, whereas NDGA does not. However, if the insects are pretreated with both compounds 20 days before subsequent infection with epimastigotes, the parasite infection is almost completely abolished. The same holds true when 5th-instar of R. prolixus are inoculated with 0.5 microg/microl/larva of both neolignans 1 day before infection. Taken together, these findings not only provide a better understanding of the lignoid function in insects, but also offer novel insights into basic physiological processes, which make lignoids interesting candidates for new types of insecticides.
Asunto(s)
Furanos , Insectos/efectos de los fármacos , Lignanos/toxicidad , Muda/efectos de los fármacos , Rhodnius/efectos de los fármacos , Trypanosoma cruzi/efectos de los fármacos , Animales , Benzofuranos , Dioxoles , Conducta Alimentaria/efectos de los fármacos , Interacciones Huésped-Parásitos , Insectos/metabolismo , Larva/efectos de los fármacos , Larva/metabolismo , Lignanos/química , Lignanos/metabolismo , Túbulos de Malpighi/efectos de los fármacos , Masoprocol , Podofilotoxina , Rhodnius/parasitología , Rhodnius/fisiología , Trypanosoma cruzi/fisiologíaRESUMEN
Acetone and ethanol extracts of the tubercula and several compounds isolated from Aristolochia pubescens (Willd) were bioassayed on velvetbean caterpillars, Anticarsia gemmatalis (Hübner), for evaluation of the insecticidal activities. Of the extracts subjected to bioassay, the acetone extract showed the highest activity. (-)-Cubebin did not show activity against soybean caterpillars, whereas aristolochic acid and ent-kaur-15-en-17-ol increased the larval period. These compounds, and (+)-eudesmin and (+)-sesamin, reduced the viability of this period, giving rise to malformed adults. These extracts and compounds are therefore potential botanical insecticide agents for the control of velvetbean caterpillars in soybean crops.
Asunto(s)
Aristolochia/química , Insecticidas/toxicidad , Larva/efectos de los fármacos , Lepidópteros/efectos de los fármacos , Extractos Vegetales/toxicidad , Animales , Ácidos Aristolóquicos/toxicidad , Bioensayo , Dioxoles/toxicidad , Diterpenos/toxicidad , Furanos/toxicidad , Lignanos/toxicidadRESUMEN
Neste estudo, os autores relatam os dados da avaliaçao dos efeitos a nível do sistema nervoso central da iangambina, uma lignana furofurânica isolada da Ocotea duckei Vattimo. Os principais efeitos observados em camundongos, foram: potencializaçao do tempo de sono induzido por pentobarbital e bloqueio das convulsoes induzidas por pentilenotetrazol.