Isolamento e avaliação do potencial citotóxico de derivados fenólicos de Schinus terebinthifolius Raddi (Anacardiaceae)

Abstract

Recebido em 27/4/12; aceito em 1/8/12; publicado na web em 25/9/12 ISOLATION AND EVALUATION OF CYTOTOXIC POTENTIAL OF PHENOLIC DERIVATIVES FROM Schinus terebinthifoliusRaddi (Anacardiaceae). The EtOH extract from leaves of S. terebinthifolius was subjected to partition between EtOH:H 2 O and hexane, CH 2 Cl 2 , and EtOAc. The phases obtained were evaluated in vitro against human tumoral cell lines and the EtOAc phase exhibited activity. Chromatographic procedures afforded gallic acid (1), methyl (2) and ethyl (3) gallates, trans-catechin (4), quercitrin (5), and afzelin (6), being the first occurrence of 1, 4 and 6 in S. terebinthifolius. In vitro cytotoxic evaluation of 1 -6 indicated that gallic acid (1) displayed higher activity than ethyl gallate (3) against HL-60 and HeLa cells, while compounds 2, 4 -6 were inactive.Keywords: Schinus terebinthifolius; phenolic derivatives; cytotoxic activity. INTRODUÇÃOSchinus terebinthifolius Raddi (Anacardiaceae) é uma árvore monoica de tamanho médio, com ocorrência em todo o território brasileiro, principalmente em regiões da Mata Atlântica.1,2 Na medicina popular, esta planta tem sido usada no tratamento de úlceras, problemas respiratórios, feridas, reumatismo, gota, diarreia, doenças de pele e artrite, 3 bem como antisséptico e anti-inflamatório. 4 Além disso, a decocção de flores, caules, frutos e folhas é utilizada para o tratamento de tumores e lepra. 5Fitoquimicamente, esta espécie produz ácidos graxos e terpenoides, principalmente os derivados ácidos 3a-masticadienoico (schinol) e masticadienoico, 6 os quais apresentam atividade inibitória da fosfolipase A2 7 além de potencial fungitóxico frente a Paracoccidioides brasiliensis.8 Derivados fenólicos, tais como os galatos de metila e etila além de flavonoides (miricetina, miricetrina e quercitrina) foram isolados do extrato polar das folhas, cuja ocorrência foi associada à elevada atividade antirradicalar.9 Adicionalmente, a análise química das cascas do tronco mostrou a existência de antraquinonas, xantonas e esteroides livres.10 Os óleos essenciais de folhas, flores e frutos de S. terebinthifolius de diferentes regiões foram previamente analisados, os quais se mostraram compostos basicamente por derivados mono e sesquiterpênicos.11 No que se refere à avaliação da atividade biológica, os óleos voláteis dos frutos foram analisados e apresentaram atividade alelopática, 12 citotóxica 13 e tripanocida, 14 enquanto que o óleo das folhas mostrou atividade citotóxica. 15Como parte de nossos estudos visando o reconhecimento de compostos com ação citotóxica em espécies vegetais brasileiras, neste trabalho foi realizado o estudo fitoquímico do extrato etanólico das folhas de S. terebinthifolius, o qual apresentou potencial in vitro frente a células tumorais humanas de melanoma (A2058), adenocarcinoma de mama (MCF7), leucemia (HL-60) e carcinoma cervical (HeLa). Após sucessivos processos de partição e purificação em gel de Sephadex LH-20 e em sílica, foi possível o isolamento do ácido gálico (1), dos galatos de metila (2) e e...

Antigenotoxic and antimutagenic effects of Schinus terebinthifolius Raddi in Allium cepa and Swiss mice: A comparative study

“…Considering the high value of total phenols and flavonoids that was found in MEST in this study and that S. terebinthifolius is essentially a tanniniferous plant, it is believed that these compounds and their derivatives (such as gallic acid) (Ceruks et al, 2007;Santana et al, 2012) have played an important antigenotoxic and antimutagenic role (Lira et al, 2008;Ben Sghaier et al, 2011;Santana et al, 2012). These phytochemicals can act as inhibitors of chemical carcinogenesis processes through antioxidant, anti-inflammatory, antimutagenic, and antitumor mechanisms of action including neutralizing free radicals, sequestering metal ions, gene expression modulation, inhibition of oxidative enzymes, and stimulation of antioxidant enzymes (Degáspari and Waszczynskyj, 2004;Lira et al, 2008;Ben Sghaier et al, 2011).…”

“…S. terebinthifolius is widely used in folk medicine to treat diseases such as ulcers, respiratory problems, wounds, rheumatism, gout, diarrhea, and tumors (Santana et al, 2012). However, its chemopreventive activity has not been reported.…”

“…In folk medicine, it is used to treat wounds and ulcers of skin and mucous membranes, tumors, diarrhea, arthritis, and infections of the urinary and respiratory systems (Morton, 1978). Some studies have shown that the medicinal properties of S. terebinthifolius are related to the high content of phenolic derivatives such as gallic acid, methyl gallate, tannins, and flavonoids that are responsible for S. terebinthifolius antioxidant and antitumor activities (Queires et al, 2006;Ceruks et al, 2007;de Mesquita et al, 2009;Santana et al, 2012). Moreover, S. terebinthifolius was included in Brazilian Pharmacopeia (Brandão et al, 2006).…”

Application of an Ionic Liquid in the Microwave Assisted Extraction of Cytotoxic Metabolites from Fruits of Schinus terebinthifolius Raddi (Anacardiaceae)

“…4 Chemically, S. terebinthifolius extracts are rich in triterpenoids, [5][6][7][8] especially tirucallane derivatives (masticadienoic acid and schinol) with anti-inflammatory, 4 antifungal 9 and antiparasitic 10 activities. Beside these compounds, phenolic derivatives such as gallic acid, methyl and ethyl gallates as well as flavonoids trans-catechin, miricetrin, miricetin, quercitrin, and afzelin, which displayed antiradical 11 and cytotoxic 12 activities, were also isolated.…”

Antiparasitic activity of natural and semi-synthetic tirucallane triterpenoids from Schinus terebinthifolius (Anacardiaceae) – Structure/activity relationships

“…Other compounds, such as phenolic derivatives (gallic acid, methyl and ethyl gallates) and flavonoids (trans-catechin, kaempferol, quercitrin, afzelin, myricetin, and myricetrin) were also isolated from the leaves and displayed antiradical and cytotoxic activities [7,8]. Chemical analysis of barks of S. terebinthifolius indicated the presence of anthraquinones, xanthones and steroids [9].…”