Naphthoquinone derivatives and lignans from the Paraguayan crude drug

Schmeda-Hirschmann,G. Laboratorio de Quımica de Productos Naturales,Instituto de Quımica de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile.The Paraguayan crude drug “tayı¨ pyta´” is used to treat cancer, wounds and inflammation. It consist of the bark and trunkwood of Tabebuia heptaphylla (Bignoniaceae). A phytochemical study of the crude drug gave, in addition to previously described naphthoquinones and the known lignans cycloolivil and secoisolariciresinol, three new lapachenol (lapachonone)-, two naphthofuran-, a chromone and a naphthalene derivative. The structures were elucidated by means of high field NMR spectroscopy. The biological activity of the main compound lapachol and the related α-lapachone as well as the lignans cycloolivil and secoisolariciresinol can explain, at least in part, the effect atributed to the crude drug in Paraguayan folk medicine

Biotransformations of imbricatolic acid by Aspergillus niger and Rhizopus nigricans cultures

Guillermo Schmeda-Hirschmann and Carlos Aranda Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile. Jaime A. Rodríguez and Cristina Theoduloz. Depto. de Ciencias Básicas Biomédicas, Facultad de Ciencias de la Salud, Universidad de Talca, Casilla 747, Talca, ChileMicrobial transformation of imbricatolic acid (1) by Aspergillus niger afforded 1α-hydroxyimbricatolic acid (2), while transformation with Rhizopus nigricans yielded 15- hydroxy-8,17-epoxylabdan-19-oic acid (3). When the diterpene 1 was added to a Cunninghamella echinulata culture, the main products were the microbial metabolites mycophenolic acid (4) and its 3-hydroxy derivative 5. All the structures were elucidated by spectroscopic methods. The cytotoxicity of these compounds towards human lung fibroblasts and AGS cells was assessed. While 4 and 5 showed low cytotoxicity, with IC50 values > 1000 μM against AGS cells and fibroblasts, 1α-hydroxyimbricatolic acid (2) presented moderate toxicity towards these targets, with IC50 values of 307 and 631 μM, respectively. The structure of 2 is presented for the first time

Anti-inflammatory, antinociceptive, and antipyretic effects of methanol extract of Cariniana rubra stem bark in animal models

Schmeda-Hirschmann, G (Schmeda-Hirschmann, Guillermo) Univ Talca, IQRN, Talca, ChileCariniana rubra Miers (Lecythidaceae), popularly known as "jequitiba-vermelho", is a large Brazilian tree whose bark is used in infusion and decoction for the treatment of inflammatory conditions. This study aims to assess the anti-inflammatory, antinociceptive, and antipyretic effects of Cariniana rubra methanolic stem bark extract (EMCr) using experimental animals. Anti-inflammatory activity of EMCr was tested on carrageenan and dextran-induced rat paw edema, carrageenan-induced pleurisy in rats and acetic acid-increase vascular permeability in mice. Antinociceptive and antipyretic activities were evaluated using acetic acid-induced writhing, formalin and hot-plate tests in mice, as well as brewer's yeast-induced pyrexia in rats. The extract inhibitied carrageenan and dextran-induced edema, reduced exudate volume and leukocyte migration on the carrageenan-induced pleurisy and on the vascular permeability increase induced by acetic acid. The EMCr inhibited nociception on the acetic acid-induced writhing and in the second phase of formalin test, and decreased rectal temperature. It was, however, inactive against thermal nociception. Phytochemical analysis with EMCr showed the occurrence of saponins, triterpenes, sterols and phenolic compounds. Phytosterols (beta-sitosterol, stigmasterol), pentacyclic triterpenes (alpha- and beta-amyrin as a mixture), arjunolic acid, a phytosterol glycoside (sitosterol 3-O-beta-D-glucopyranoside), and triterpenoid saponins (28-beta-glucopyranosyl-23-O-acetyl arjunolic acid; 3-O-beta-glucopyranosyl arjunolic acid and 28-O-[alpha-L-Rhamnopyranosyl-(1 -> 2)-beta-glucopyranosyl]-23-O-acetyl arjunolic acid) were the main identified compounds. It can be presumed that EMCr caused their effects by inhibiting the liberation and/or action of different inflammatory mediators. These findings support the traditional use of Cariniana rubra preparations to treat inflammation

Total synthesis of the Amaryllidaceae alkaloid clivonine

Two syntheses of the Amaryllidaceae alkaloid clivonine (1) are described. Both employ previously reported 7-arylhydrindane 6 as an intermediate but differ in the method employed for subsequent introduction of what becomes the ring-B lactone carbonyl carbon (C7). The synthesis featuring a Bischler–Napieralski reaction for this transformation constitutes the first asymmetric synthesis of natural (+)-clivonine. Crystal structures for compounds (±)-13, (±)-16, (−)-20 and (±)-28 are also reported

Analysis of the Aspergillus fumigatus Proteome Reveals Metabolic Changes and the Activation of the Pseurotin A Biosynthesis Gene Cluster in Response to Hypoxia

The mold Aspergillus fumigatus is the most important airborne fungal pathogen. Adaptation to hypoxia represents an important virulence attribute for A. fumigatus. Therefore, we aimed at obtaining a comprehensive overview about this process on the proteome level. To ensure highly reproducible growth conditions, an oxygen-controlled, glucose-limited chemostat cultivation was established. Two-dimensional gel electrophoresis analysis of mycelial and mitochondrial proteins as well as two-dimensional Blue Native/SDS-gel separation of mitochondrial membrane proteins led to the identification of 117 proteins with an altered abundance under hypoxic in comparison to normoxic conditions. Hypoxia induced an increased activity of glycolysis, the TCA-cycle, respiration, and amino acid metabolism. Consistently, the cellular contents in heme, iron, copper, and zinc increased. Furthermore, hypoxia induced biosynthesis of the secondary metabolite pseurotin A as demonstrated at proteomic, transcriptional, and metabolite levels. The observed and so far not reported stimulation of the biosynthesis of a secondary metabolite by oxygen depletion may also affect the survival of A. fumigatus in hypoxic niches of the human host. Among the proteins so far not implicated in hypoxia adaptation, an NO-detoxifying flavohemoprotein was one of the most highly up-regulated proteins which indicates a link between hypoxia and the generation of nitrosative stress in A. fumigatus