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

Preparación de moléculas híbridas con potencial antiinflamatorio

33 p.Las úlceras gástricas tienen gran importancia a nivel mundial debido a su prevalencia y especialmente a las consecuencias que puede llegar a presentar, como es el cáncer gástrico. Chile se encuentra entre los países con mayor prevalencia de cáncer gástrico, destacándose los índices de prevalencia de esta enfermedad en la región de Maule. En el tratamiento de las úlceras gástricas se emplean diversos fármacos, además de recomendaciones dietéticas. Entre estos fármacos hay compuestos de origen natural asociados a patentes, principalmente en Japón. En Chile, se ha demostrado el efecto gastroprotector de distintos compuestos naturales, la gran mayoría de ellos en la Universidad de Talca. Entre los distintos estudios originados en la Universidad de Talca, destacamos los realizados con diterpenos obtenidos de la resina de Araucaria araucana y con el diterpeno ferruginol obtenido de Prumnopitys andina (Lleuque). Se conoce muy poco sobre los efectos que se producirían al combinar dos unidades diferentes con efecto biológico complementario en una molécula única, llamadas “compuestos híbridos”. En el presente trabajo, se prepararon nuevos compuestos híbridos, uniendo diterpenos con los antiinflamatorios sintéticos ibuprofeno y naproxeno. Se consiguió la síntesis exitosa de 3 nuevas moléculas híbridas, que son ésteres de un ácido aromático (ibuprofeno o naproxeno) y el diterpeno fer6ruginol con una función alcohol. También se obtuvo una amida uniendo ácido antranílico con ácido junicédric

Fabiana imbricata Ruiz et Pay. (Solanaceae), a review of an important Patagonian medicinal plant. Review

Ethnopharmacological relevance: Fabiana imbricata (Solanaceae) is a Patagonian medicinal plant with a long tradition of use. The aim of this review is to provide an integrative overview of the traditional uses, chemistry, bioactivity and chemical profiling of the crude drug. Materials and methods: The information was collected from scientific databases searching with the keywords Fabiana imbricata, Fabiana species, Fabiana (Solanaceae) and includes local literature and books. Results: The indications of use reported in literature show little variation from the data published as early as 1889. The chemical studies showed a rich diversity in metabolites including phenolics, coumarins, flavonoids, phenylpropanoids, terpenes, alkaloids and sugars. Bioactivity studies supported the traditional use as diuretic and also the potential of the crude drug as a gastroprotective agent. The plant can be used as a source of compounds with effect on gastric ulcers and shows enzyme inhibitory activity. While the germination rate of the plant is very low, protocols were developed for the rapid in vitro propagation of the species. The toxicity of the crude drug extracts was low and did not show clastogenic effect in human lymphocytes. Further research is needed to disclose the potential of the F. imbricata sesquiterpenes on other relevant biological targets

DESMIDS SACCODERMAE AND PLACODERMAE OF CHILE 4. DESMIDS OF THE LAKES SYSTEM OF CORDILLERA-DEL-PAINE AND PROXIMITY

Volume: 41Start Page: 201End Page: 22

Xanthine oxidase inhibitory activity of Chilean Myrtaceae

Cristina Theoduloz, Patricia Pacheco and Guillermo Schmeda-Hirschmann Facultad de Recursos Naturales, Departmento de Ciencias Biológicas, Universidad de Talca, Casilla 747, Talca, Chile.Twenty-one Myrtaceae collections belonging to 10 species, 5 of which are used in Chilean folk medicine, were assayed for inhibitory activity towards the enzyme xanthine oxidase. Most leaf and stem extracts were devoid of activity or showed a weak inhibitory effect. Chilean ethnobotanical data on the species arc linked to the astringent properties of Myrtaceae and their use for treating wounds and diarrhea. The results show the advantage of using proper plant selection criteria when searching for new drugs to treat human gout

Effect of Fabiana imbricata constituents on Rhopalosiphum padi and Heliothis zea

G. Schmeda-Hirschmann, P. Román , C. Theoduloz. Departamento de Ciencias Biológicas, Universidad de Talca, Casilla 747, Talca, Chile.The main secondary metabolites of Fabiana imbricata showed toxicity towards the greenbug Rhopalosiphum padi when administered in an artificial diet. A dose-dependent toxicity was observed for fabiaimbricatan-15-oic acid and oleanolic acid at doses up to 3.0 mM (p <0.01). Both compounds apparently act as antifeedants at higher doses. Rutin also showed a dose-related toxicity. Scopoletin and p-hydroxyacetophenone were toxic at 6.0 mM. None of the compounds tested were toxic towards the fifth instar Heliothis zea larvae

New diterpene and heterocycles hybrid compounds: Synthesis and gastroprotective mechanisms of action using human cell cultures

Meeting Abstrac

Antiproliferative activity of arborescidine alkaloids and derivatives

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Current issues in cancer research involve searching for novel anticancer compounds that can be used to regulate the cell cycle and lead to more effective treatments of tumors. In this study, it was hypothesized that possessing a cyclic alkaloid similar to harmine, arborescidines can disrupt the proliferative state of cancer cells and block the activity of topoisomerases. The antiproliferative activity of arborescidines A-C and their derivatives was evaluated in vitro against four human tumor cell lines: gastric adenocarcinoma, lung cancer, bladder carcinoma and leukemia. Assuming the mechanism of action by topoisomerase II binding model, the compounds possessing the greatest activity had nonpolar side-chain into hydrophobic binding region on the DNA/topo II complex. (C) 2009 Elsevier Masson SAS. All rights reserved.44938103815FONDECYT [1085308, 1060841]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)IFS [F/4195-1]Organisation for the Prohibition of Chemical WeaponsPrograma de Investigacion 3815 en Productos Bioactivos-UTalcaFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FONDECYT [1085308, 1060841]IFS [F/4195-1

Gastroprotective effect and cytotoxicity of terpenes from the Paraguayan crude drug “yagua rova” (Jatropha isabelli)

Mariano Pertinoa and Guillermo Schmeda-Hirschmann. 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. Departamento de Ciencias Básicas Biomédicas, Facultad de Ciencias de la Salud, Universidad de Talca, Casilla 747, Talca, ChileA new jatrophone derivative (6), jatrophone (3), jatropholone A (4) and jatropholone B (5), acetyl aleuritolic acid (1), cyperenoic acid (2) and a monoterpene were isolated from the rhizomes of the Paraguayan crude drug Jatropha isabelli. The compounds were characterized by spectroscopic means. The gastroprotective effect of jatrophone, jatropholone A and B as well as 9β,13-dihydroxyisabellione 6 and the triterpene 1 was assessed in the HCl/EtOH-induced gastric lesions model in mice. Jatrophone elicited a strong gastroprotective effect with no significant differences between 25, 50 or 100 mg/kg and reducing lesions from 88 to 93%. The jatropholones A and B showed remarkable differences in the gastroprotective assay. Jatropholone A presented a dose-related response, with maximum effect (54% lesion reduction) at the highest dose (100 mg/kg), jatropholone B showed a strong action at all the doses, reducing lesions by 83–91%. The cytotoxicity of the compounds was assessed towards fibroblasts and AGS cells. Jatrophone was toxic against both cell lines (IC50 values: 2.8 and 2.5 μM, respectively). Jatropholone B (5) was not cytotoxic while jatropholone A (4) displayed a selective effect against AGS cells (IC50: 49 μM). The relevance of stereochemistry in the biological effects is clear comparing the effect of jatropholone A and B against AGS cells, with IC50 values of 49 and >1000 μM for the β and C-16 isomers, respectively. The results provide scientific support for the use of “yagua rova” as a gastroprotective crude drug in Paraguayan traditional medicine