1H and 10B NMR and MRI investigation of boron- and gadolinium-boron compounds in boron neutron capture therapy.

(10)B molecular compounds suitable for Boron Neutron Capture Therapy (BNCT) are tagged with a Gd(III) paramagnetic ion. The newly synthesized molecule, Gd-BPA, is investigated as contrast agent in Magnetic Resonance Imaging (MRI) with the final aim of mapping the boron distribution in tissues. Preliminary Nuclear Magnetic Resonance (NMR) measurements, which include (1)H and (10)B relaxometry in animal tissues, proton relaxivity of the paramagnetic Gd-BPA molecule in water and its absorption in tumoral living cells, are reported.

In vitro hepatoprotective and antioxidant activities of crude extract and isolated compounds from Ficus gnaphalocarpa.

The in vitro hepatoprotective effect of the methanolic extract from Ficus gnaphalocarpa (Miq.) Steud. ex A. Rich (Moraceae) on the CCl4-induced liver cell damage as well as the possible antioxidant mechanisms involved in this protective effect, were investigated. The phytochemical investigation of this methanolic extract led to the isolation of six compounds identified as: betulinic acid (1); 3-methoxyquercetin (2); catechin (3); epicatechin (4); quercetin (5); and quercitrin (6). The hepatoprotective activity of these compounds was tested in vitro against CCl4-induced damage in rat hepatoma cells. In addition, radical-scavenging activity, ß-carotene-linoleic acid model system, ferric-reducing antioxidant parameter and microsomal lipid peroxidation assays were used to measure antioxidant activity of crude extract and isolated compounds. Silymarin and trolox were used as standard references and, respectively, exhibited significant hepatoprotective and antioxidant activities. (5), (6) and (2) showed significant antioxidant and hepatoprotective activities as indicated by their ability to prevent liver cell death and lactate dehydrogenase leakage during CCl4 intoxication. These results suggest that the protective effects of crude extract of F. gnaphalocarpa against the CCl4-induced hepatotoxicity possibly involve the antioxidant effect of these compounds.

Anti-secretory, anti-inflammatory and anti-Helicobacter pylori activities of several fractions isolated from Piper carpunya Ruiz & Pav.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Piper carpunya Ruiz & Pav. (syn Piper lenticellosum C.D.C.) (Piperaceae), are widely used in folk medicine in tropical and subtropical countries of South America as an anti-inflammatory, anti-ulcer, anti-diarrheal and anti-parasitical remedy as well as an ailment for skin irritations. AIMS OF THE STUDY: To study the anti-inflammatory, anti-secretory and anti-Helicobacter pylori activities of different fractions isolated from an ethanolic extract of the leaves of Piper carpunya, in order to provide evidence for the use of this plant as an anti-ulcer remedy. Moreover, to isolate the main compounds of the extract and relate their biological activity to the experimental results obtained with the fractions. MATERIALS AND METHODS: Sixteen fractions were obtained from the ethanolic extract (F I-XVI) and 16 pure compounds were isolated and identified from these fractions. We studied the effects of the fractions (0.1-400microg/mL) on the release of myeloperoxidase (MPO) enzyme from rat peritoneal leukocytes, on rabbit gastric microsomal H(+), K(+)-ATPase activity and anti-Helicobacter pylori anti-microbial activity using the microdilution method (MM). The main compounds contained in the fractions were isolated and identified by (1)H- and (13)C NMR spectra analysis and comparison with the literature data. RESULTS: Eight fractions showed inhibition of MPO enzyme (F I-IV, X, XII, XIV and XV). The highest inhibition was observed with F XIV (50microg/mL, 60.9%, p<0.001). F X and XII were the most active ones, inhibiting the gastric H(+), K(+)-ATPase activity with IC(50) values equal to 22.3microg/mL and 28.1microg/mL, respectively. All fractions, except F XV, presented detectable anti-Helicobacter pylori activity, with a diameter of inhibition zones ranging from 11mm up to 50mm. The best anti-Helicobacter pylori activity was obtained with F III and V. Both fractions killed Helicobacter pylori with lowest concentration values, about 6.25mug/mL. Sixteen pure compounds were isolated, five of them are flavonoids that possess strong anti-oxidant and free radical scavenging activity, e.g. vitexin, isovitexin, and rhamnopyranosylvitexin. Terpenoids like sitosterol, stigmasterol and phytol, which have shown gastroprotective activity, and dihydrochalcones, like asebogenin, with anti-bacterial activity, were also isolated. Furthermore, the rare neolignan 1, that is a DNA polymerase beta lyase inhibitor, and (6S, 9S)-roseoside, that shows strong anti-bacterial activity, were isolated, for the first time, from the genus Piper. CONCLUSIONS: We suggest that the flavonoids isolated from F I and II (vitexin, isovitexin, rhamnopyranosylvitexin and isoembigenin) contribute to the anti-MPO activity, as well as to their anti-Helicobacter pylori activity. These flavonoids may also be responsible for the important inhibition of H(+), K(+)-ATPase activity. Also the phytosterols and phytol obtained from F XIV and XV could be involved in these gastroprotective activities. These results encourage us to continue phytochemical studies on these fractions in order to obtain full scientific validation for this species.

Putrescine-1,4-dicinnamide from Pholiota spumosa (Basidiomycetes) inhibits cell growth of human prostate cancer cells.

Previously, it was isolated from the fruiting bodies of the gilled mushroom Pholiota spumosa (Basidiomycetes, Strophariaceae), putrescine-1,4-dicinnamide, a phenylpropanoid derivative conjugated with polyamine putrescine never isolated before as a natural compound. Recently, polyamine analogs that are similar in structure to the natural polyamines but that cannot mimic their functions that are essential for cellular growth and differentiation, have shown antitumor activity in several types of human cancer cells. Therefore, we have now investigated the response of DU-145 cells, a well characterized androgen-independent human prostate cancer (PCA) cell line, to this phenylpropanoid derivative. The results presented here demonstrate that putrescine-1,4-dicinnamide, as suggested for polyamine analogs synthesized artificially, inhibits the cell growth of cancer cells inducing apoptosis cell death, mediated, at least in part, by the activation of caspase cascades, that at higher doses shift to necrosis, through the increase of reactive oxygen species (ROS) generation.

A bioactive tetraprenylphenol from Lactarius lignyotus.

2-Geranylgeranyl-1,4-dihydroxybenzene [1] and a mixture of fatty acid esters of this phenol were isolated from the fruiting bodies of Lactarius lignyotus. Compound 1 was highly active in the brine shrimp test and showed significant inhibitory activity on DNA, RNA, and protein synthesis in HeLa and HL-60 cell lines.

New fatty acid esters of drimane sesquiterpenes from Lactarius uvidus.

This study of lipids of Lactarius uvidus has revealed the presence of new fatty acid esters of uvidin A [2a-d] and drimenol [6a-d]. Treatment of uvidin A [1] with base induced a Favorskii-like rearrangement leading to compounds with a new sesquiterpenoid skeleton. Uvidin A [1] showed insect antifeedant and cytotoxic activities.

Constituents of essential oil of Aframomum giganteum.

The composition of the essential oil of Aframomum giganteum was investigated by GC-MS. Forty seven terpenes were identified, the oil contained a high percentage of linalool and linalyl acetate which are mainly responsible for the smell of the A. giganteum stems. Fatty acids, paraffins, n-octanol, n-nonanol and guaiacol were also identified.