Ivan de Oliveira Pereira

Leishmanicidal activity of benzophenones and extracts from Garcinia brasiliensis Mart. fruits

Infections by protozoans of the genus Leishmania are the major worldwide health problem, with high endemicity in developing countries. The drugs of choice for the treatment of leishmaniasis are the pentavalent antimonials, which exert renal and cardiac toxicity. Thus, there is a strong need for safer and more effective treatments against leishmaniasis. The present study was designated to evaluate, by a bioguided assay, the leishmanicidal activity of extracts (hexane, ethyl-acetate and ethanolic) and molecules both obtained by means of extraction from pericarps of Garcinia brasiliensis fruits. The hexane extract presented the best activity on the extracellular (promastigotes) and intracellular (amastigotes) forms of Leishmania (L.) amazonensis, when compared to the other extracts. Based on these findings, this extract was fractionated by silica gel column chromatography, affording nine fractions then resulting in three purified prenylated benzophenones - 7-epi-clusianone (1), garciniaphenone (2) and guttiferone-a (3). They showed significant activity on Leishmania (L.) amazonensis, and little toxicity for mammalian cells. Structure-activity relationships were evaluated showing that the IC(50) value displayed is dependent of prenyl groups and phenolic hydroxyls number, and inversely proportional to the hydrophobicity. Our results are promising, showing that these compounds are biologically active on Leishmania (L.) amazonensis.

Natural Products from Garcinia brasiliensis as Leishmania Protease Inhibitors

The infections by protozoans of the genus Leishmania are a major worldwide health problem, with high endemicity in developing countries. The drugs of choice for the treatment of leishmaniasis are the pentavalent antimonials, which cause renal and cardiac toxicity. As part of a search for new drugs against leishmaniasis, we evaluated the in vitro Leishmania protease inhibition activity of extracts (hexanic, ethyl-acetate, and ethanolic) and fukugetin, a bioflavonoid purified from the ethyl-acetate extract of the pericarp of the fruit of Garcinia brasiliensis, a tree native to Brazilian forests. The isolated compound was characterized by using spectral analyses with nuclear magnetic resonance, mass spectroscopy, ultraviolet, and infrared techniques. The ethyl-acetate extract and the compound fukugetin showed significant activity as inhibitors of Leishmanias proteases, with mean (±SD) IC(50) (50% inhibition concentration of protease activity) values of 15.0±1.3 μg/mL and 3.2±0.5 μM/mL, respectively, characterizing a bioguided assay. In addition, this isolated compound showed no activity against promastigote and amastigote forms of L. (L.) amazonensis and mammalian cells. These results suggest that fukugetin is a potent protease inhibitor of L. (L.) amazonensis and does not cause toxicity in mammalian or Leishmania cells in vitro. This study provides new perspectives on the development of novel drugs that have leishmanicidal activity obtained from natural products and that target the parasites proteases.

Inhibition of cysteine proteases by a natural biflavone: behavioral evaluation of fukugetin as papain and cruzain inhibitor

Cruzain is the major cysteine protease of Trypanosoma cruzi, the infectious agent responsible for Chagas disease, and cruzain inhibitors display considerable antitrypanosomal activity. In the present work we elucidated crystallographic data of fukugetin, a biflavone isolated from Garcinia brasiliensis, and investigated the role of this molecule as cysteine protease inhibitor. The kinetic analyses demonstrated that fukugetin inhibited cruzain and papain by a slow reversible type inhibition with KI of 1.1 and 13.4 µM, respectively. However, cruzain inhibition was about 12 times faster than papain inhibition. Lineweaver–Burk plots demonstrated partial competitive inhibition for cruzain and hyperbolic mixed-type inhibition for papain. Furthermore, the docking results showed that the biflavone binds to ring C′ in the S2 pocket and to ring C in the S3 pocket through hydrophobic interactions and hydrogen bonds. Finally, fukugetin also presented inhibitory activity on proteases of the T. cruzi extract, with IC50 of 7 µM.

Atividade antiinflamatória de carboidrato produzido por fermentação aquosa de grãos de quefir

Kefir, a symbiont microorganism suspension, presents benefic effects to health. Some kefir grains were cultivated in brown sugar, allowing to isolate a substance named CSQ. This was evaluated on a biologic essay of mouse foot edema, presenting an inhibitory activity of 30+4 % against carrageenan after the stimulus. It was observed that a cultivation mean containing sucrose, and not the milky mean, lead to the production of different sugar polymeric chains of kefir. The results in vivo suggest that the CSQ exerted an anti-inflammatory activity.

Leishmanioses: "estado da arte"

There is no vaccine available against leishmaniasis. Drug resistance, variable efficacy, toxicity, parenteral administration, and requirement for long courses of administration are the main drawbacks of current leishmanicidal drugs. Infections by protozoans of the genus Leishmania are the major worldwide health problem, with high endemicity in developing countries. The drugs of choice for the treatment of leishmaniasis are the pentavalent antimonials, which exert renal and cardiac toxicity, thus, there is a strong need for safer and more effective treatments against leishmaniasis.

BIO079 Oligopeptidases B and C from trypanosomatids as therapeutic targets for natural products

Infections caused for trypanosomatids represent one of the biggest problems of world-wide public health, with high endemicit over all in developing countries. The drugs of choice for the treatment of these parasitisms, general way, cause well-known renal and cardiac toxicity, beyond inducing resistance in the parasite and many times to present insufficient effectiveness.

PNS017 Enzyme inhibition in trypanosomatids: a therapeutic target for crude extracts and fractions of natural products

Infections caused by trypanosomatids of Leishmania genus represent one of the largest global public health problems, currently with high endemicity especially in developing countries. The drugs of choice for the treatment of leishmaniasis are the pentavalent antimonials, which cause renal and cardiac toxicity, and induce resistance in the parasite.

AVALIAÇÃO “IN VITRO” DA ATIVIDADE ANTIMICROBIANA DA BENZIDAMINA

Com o objetivo de avaliar a provavel atividade antibacteriana e antifungica da benzidamina, determinou-se a Concentracao Inibitoria Minima e a Concentracao Bactericida/Fungicida Minima, sobre varias amostras de microrganismos. Foram usadas as tecnicas de difusao no agar (tecnica do poco) e a da diluicao em tubo. A avaliacao da sensibilidade dos microrganismos a benzidamina, na tecnica do poco, foi feita pela leitura dos halos de inibicao e na tecnica de diluicao em tubo, pela inibicao do crescimento. Os resultados mostraram que a benzidamina possui atividade antimicrobiana sobre as amostras de leveduras e bacterias testadas. Comparando as duas tecnicas verificou-se que pela tecnica de difusao em agar, o valor da concentracao inibitoria minima (CIM) foi maior do que pela tecnica de diluicao em tubo.