Antitumoral, mutagenic and (anti)estrogenic activities of tingenone and pristimerin

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Trypanocidal activity of quinonemethide triterpenoids from Cheiloclinium cognatum (Hippocrateaceae)

We report the trypanocidal activity of quinonemethide triterpenoids isolated from root extracts of Cheiloclinium cognatum, a plant of the Hippocrateaceae family, collected in the Cerrado Reserve at Universidade Federal de Goias, Brazil. The trypanocidal activity assays showed an effect on the blood trypomastigote forms of the Y strain of Trypanosoma cruzi where tingenone and tingenol demonstrated activity on the parasite. Their structures were elucidated on the basis of spectral data, particularly COSY, HMQC and HMBC experiments, and chemical transformations.

Anti-trypanosomal activity of pentacyclic triterpenes isolated from Austroplenckia populnea (Celastraceae)

Four pentacyclic triterpenes isolated from Austroplenckia populnea and four compounds of known anti T. cruzi or anti-malarial activity were tested. Of those triterpenes tested 20alpha-hydroxy-tingenone showed high activity, epikatonic acid was less active, while populnilic and populninic acids were inactive against the trypanosome of the subgenus Schizotrypanum tested. Benzonidazole, nifurtimox, ketoconazole and primaquine presented a remarkable dose-dependent inhibitory effect reaching practically to a total growth inhibition of the parasite at the end of incubation time. The trypanosome tested appear to be a suitable model for preliminary screen for anti T. (S.) cruzi compounds.

Evaluation of antimicrobial activity and toxic potential of extracts and triterpenes isolated from Maytenus imbricata

The phytochemical study of hexane/ethyl ether (1:1) extract of the roots of M. imbricata, Celastraceae, resulted in the isolation and characterization of six known triterpenes: 11α-hydroxylup-20(29)-en-3-one, previously isolated from this species besides, 3β,11α-di-hydroxylup-20(29)-ene, 3,7-dioxofriedelane, 3-oxo-29-hydroxyfriedelane, tingenone and 6-oxo-tingenol. The chemical structures of these triterpenes were established by spectrometric data (IR, ¹H and 13C NMR) and through comparison with literature data. The hexane/ethyl ether (1:1), ethyl acetate and methanol extracts, and 11α-hydroxylup-20(29)-en-3-one, tingenone and 6-oxo-tingenol, showed antimicrobial properties on in vitro assays. All extracts and triterpenes, except 3β,11α-di-hydroxylup-20(29)-ene, presented toxicity demonstrated by the larvicidal effect test using Artemia salina.

Release of intermediate reactive hydrogen peroxide by macrophage cells activated by natural products

By determining the hydrogen peroxide (H2O2) released in cultures of peritoneal macrophage cells from Swiss mice, we evaluated the action of 27 vegetable compounds (pristimerin, tingenone, jatrophone, palustric acid, lupeol, cladrastin, ocoteine, boldine, tomatine, yohimbine, reserpine, escopoletin, esculine, plumericin, diosgenin, deoxyschizandrin, p-arbutin, mangiferin, and others) using a 2 mg/ml solution of each compound (100 mug/well). Macrophages are cells responsible for the development of the immunological response reaction, liberating more than one hundred compounds into the extracellular environment. Among these are the various cytokines and the intermediate compounds of nitrogen (NO) and oxygen (H2O2). This coordinated sequence of biochemical reactions is known as the oxidative burst. When we compared the results with those obtained with zymosan (an important stimulator of H2O2) we observed that the compounds showing the highest activity were substances 2 (tingenone), 16 (reserpine) and 20. Other substances such as compounds 1, 4, 5, 6, 8, 12, 13, 14, 15, 17, 19, 23, 24, 26, and 27 also showed a certain activity, but with less intensity than the aforementioned ones. Compounds 3, 7, 9, 10, 11, 18, 21, 22 and 25 presented no activity. These results suggest that natural products (mainly tingenone and reserpine and others) with different chemical structures are strong immunological modulators. However, further tests are needed to determine the 'oxidative burst' in future studies.

Pesquisa de atividade antitumoral e mutagênica in vitro de produtos naturais

Pós-graduação em Ciências Farmacêuticas - FCFAR