The interaction of a thiosemicarbazone derived from R - (+) - limonene with lipid membranes.

As a potential drug, 2-nitrobenzaldehyde-thiosemicarbazone (2-TSC), a thiosemicarbazone derived from the terpene R-(+)-limonene, was studied through calorimetric and spectroscopic techniques. Differential Scanning Calorimetry (DSC) data showed that 2-TSC causes structural changes in a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DMPC) membrane, strongly decreasing the cooperativity of the bilayer gel-fluid thermal transition. Optical absorption spectroscopy showed that 2-TSC is more soluble in ethanol and lipids than in water medium, and that the drug displays different structures in the different environments. Though 2-TSC displays no fluorescence, time resolved fluorescence showed that the drug is an effective quencher of the fluorescent probe 6-dodecanoyl-2-dimethylaminonaphthalene (Laurdan). As it is well accepted that Laurdan is positioned into the bilayer close to the membrane surface, that is possibly the localization of 2-TSC in a bilayer. Electron spin resonance (ESR) of the probe 1-palmitoyl-2-stearoyl-(14-doxyl)-sn-glycero-3-phosphocholine (14-PCSL) revealed that 2-TSC is inserted into the hydrocarbon part of the bilayer, fluidizing the lipid bilayer gel phase and rigidifying or organizing the bilayer fluid phase. Similar effects are found for other lipophilic molecules, including cholesterol. These results are useful to improve the understanding of the processes that govern the interaction of thiosemicarbazones with cell membranes, related to the activity of the drugs and their cytotoxicity.

Assessment of toxic, genotoxic, antigenotoxic, and recombinogenic activities of Hymenaea courbaril (Fabaceae) in Drosophila melanogaster and mice.

Hymenaea courbaril L., popularly known as jatobá, is a plant species that grows in the forests of South America. The species has been used for culinary purposes and in folk medicine to treat arthritis and inflammations. Due to the increasing use of this plant globally, the present study aimed to evaluate the toxic, genotoxic, recombinogenic, and antigenotoxic effects of H. courbaril sap (Hycs) using the mouse bone marrow micronucleus test and the somatic mutation and recombination test (SMART) in Drosophila melanogaster. To evaluate the aneugenic and clastogenic activities revealed by the micronucleus test, the animals were treated with 3 doses of Hycs (5, 10, and 15 mL/kg body weight). To evaluate the antianeugenic and anticlastogenic activities, the animals were simultaneously treated with Hycs and mitomycin C (4 mg/kg body weight). To assess the mutagenic and recombinogenic activities using SMART, 3-day-old larvae derived from standard and high bioactivation crosses were treated with 3 doses of Hycs (3.0, 1.5, and 0.3 mL) for approximately 48 h. To evaluate antimutagenic and antirecombinogenic activities, larvae derived from both crosses were co-treated with 3 doses of Hycs (3.0, 1.5, and 0.3 mL) and doxorubicin (0.125 mg/ mL). The mouse bone marrow micronucleus test revealed that Hycs exhibited no cytotoxic, clastogenic and/or aneugenic effects, but did show anticytotoxic, anticlastogenic and/or antianeugenic activities. The SMART revealed no mutagenic or recombinogenic effects, but antimutagenic and antirecombinogenic activities were observed in somatic cells of D. melanogaster from both crosses.

Diuretic activity and acute oral toxicity of Palicourea coriacea (Cham.) K Schum.

AIM OF THE STUDY: Palicourea coriacea (Cham.) K Schum, is an endemic plant used in the Midwestern Region of Brazil, popularly known as "douradinha do campo" and "congonha do campo". This plant has been used in traditional medicine for several ailments, especially to treat kidney diseases. Since no formal studies on the biological activities and medicinal properties of the ethanolic extract of Palicourea coriacea (PCEE) have been carried out previously, the present study represents the first research into the efficacy of this plant as a diuretic agent employing laboratory rats as test animals. MATERIALS AND METHODS: For diuretic activity evaluation we assayed three doses of PCEE (20, 40 and 80mg/kg) and measurement of the urinary volume and electrolytes (Na(+), K(+)) concentration were taken. The acute oral toxicity of PCEE was investigated according to OECD Guideline 423. RESULTS: The oral administration of a single dose of PCEE significantly increased the urinary volume in 24h. Additionally, the treatment with PCEE increased, in a dose-dependent manner, the excretion of both, Na(+) and K(+). No sign of toxicity was observed in the animals. CONCLUSIONS: The present study confirmed the ethnopharmacological use of Palicourea coriacea as a diuretic agent in the experimental condition tested here. Additionally, this work supports the importance of the preservation of local knowledge as well as the conservation of Brazilian biodiversity.

Antiproliferative activity of Pterodon pubescens Benth. seed oil and its active principle on human melanoma cells.

On a preliminary screening, relevant in vitro antiproliferative activity was observed to the crude ethanolic extract of Pterodon pubescens seed oil against the human melanoma cell line SK MEL 37. The diethyl ether fraction from crude ethanolic extract which exhibited stronger activity was submitted to fractionation by gradient elution with hexane/ethyl acetate. Subfraction A, eluted by hexane/ethyl acetate (80:20), was essentially the most active between all the assayed subfractions with an IC(50) of 37microg/ml calculated by the MTT colorimetric method. At this concentration, subfraction A caused morphological features and internucleosomal DNA fragmentation pattern of apoptosis. Through chromatographic separation, the furane diterpene 1 was isolated from this active subfraction and identified by spectral techniques. Compound 1 showed an IC(50) value of 32microM and fluorescence staining with DAPI revealed some typical nuclear changes which are characteristic of apoptosis. These findings support a role for diterpenoids vouacapan-type skeleton as a model to develop new anticancer agents.