Isolamento, caracterização estrutural e avaliação do potencial farmacológico de metabólitos especiais das folhas de Schinus terebinthifolius (Anacardiaceae)

• Ano de defesa: 2014
• Autor(a) principal: Morais, Thiago Rahal [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo
• Palavras-chave em Português: Schinus terebinthifolius; (Z)-masticadienoic acid; (Z)-schinol; Chemical structure/biological activity; Cytotoxic activity; Antiparasitic activity; Ácido (Z)-masticadienóico; Estrutura química/atividade biológica; Atividade citotóxica; Atividade antiparasitária
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=1361253; http://repositorio.unifesp.br/handle/11600/47751

The present work was performed a bioguided phytochemical study by antiparasitic and cytotoxic activities of extracts from leaves of Schinus terebinthifolius Raddi (Anarcadiaceae). Initially, this extract showed in vitro cytotoxic potential against the murine melanoma cell line B16F10-Nex2 (IC50 of 82 ± 5g/mL) and antiparasitic activity against amastigotes and promastigotes of Leishmania infantum (100% killing 300g/mL) and Trypanosoma cruzi trypomastigotes (90% kill at 300g/mL). After partition, it was found that the activities were concentrated in the hexane phase which underwent successive purification procedures (silica gel and Sephadex LH-20) fully monitored by bioassay. Thus, two triterpenes were isolated bioactive tirucalanes, whose structures were defined as the (Z)-masticadienoic acid (1) and (Z)-schinol (2) after NMR analysis. After isolation, the compounds 1 and 2 were evaluated against different human tumor cell lines (A2058: melanome, HeLa: cervical carcinome, HCT: colon tumor; SKBR-3: breast cancer and U87: glioblastome) whose IC50 values ranged between > 150-32 ± 3g/mL, being the most active compound 2. With regard to the antiparasitic activity, the results showed that compound 1 is inactive against the promastigotes of L. infantum but has moderate activity for amastigotes with IC50 of 66.51 g/mL compared to positive control (miltefosine - EC50 of 7.25g/mL). Regarding the compound 2, also lack of activity against promastigostes and weak forms potential against amastigotes of L. infantum (EC50 97.59g/mL) was observed. When the two compounds were evaluated for activity against T. cruzi trypomastigotes, it was observed that 1 is inactive (EC50 > 150g/mL) while excellent potential was detected for 2 with EC50 of 16.28g/mL, compared to standard drug (benznidazole) whose EC50 value was determined to be 114.68g/mL. Compounds 1 and 2 showed reduced toxicity front NCTC the cells with CC50 values of > 200 and 95.49g/mL, respectively. In order to establish correlations chemical/biological activity of eight derivatives structure based on the structure 1 by acetylation and reduction reactions of the carbonyl group at C-3, methylation of the carboxylic acid (C-27) were prepared, and hydrogenation of double bond at C-24. After evaluation of the cytotoxic activity was observed that the reduced and acetylated at C-3 substance was best presented result against the human strains tested with IC50 values ranging from 11 ± 1 to 17 ± 1g/mL. Regarding the antiparasitic activity was detected that all semisynthetic derivatives are less active than the natural products 1 and 2, indicating that the presence of the hydroxyl group at C-3 is essential for antitrypanosomal activity while the carbonyl group in the same position is important for potential antileishmanial. Based on the results obtained, it can be inferred that the triterpenes 1 and 2, isolated from S. terebinthifolius can be used as a prototype for the development of new drugs for cancer treatment, as well as the Chagas disease and leishmaniasis.