Natural and semi-synthetic clerodanes of Croton cajucara and their cytotoxic effects against ehrlich carcinoma and human K562 leukemia cells
| Autor: | Jenilce R. Martins, Maria Aparecida Medeiros Maciel, Angelo C. Pinto, Carlos R. Kaiser, Aurea Echevarria, Andressa Esteves-Souza |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | Journal of the Brazilian Chemical Society v.18 n.2 2007 Journal of the Brazilian Chemical Society Sociedade Brasileira de Química (SBQ) instacron:SBQ Journal of the Brazilian Chemical Society, Volume: 18, Issue: 2, Pages: 391-396, Published: APR 2007 |
| ISSN: | 0103-5053 |
| DOI: | 10.1590/s0103-50532007000200022 |
| Popis: | The clerodane-type diterpene, trans-dehydrocrotonin (1) the major component of Croton cajucara has shown striking correlation with its therapeutic use in traditional folk medicine. Phytochemical investigations led to the isolation of the metabolites 1, cajucarinolide (6), isocajucarinolide (7), trans-crotonin (2), trans-cajucarin B (3), cis-cajucarin B (4), trans-cajucarin A (5), N-methyltyrosine, vanillic acid and 4-hydroxy-benzoic acid. 6 and 7 were synthesized in good yield by regiospecific oxidation of 1 using singlet-oxygen. All clerodanes were studied for their cytotoxic effects against human K562 leukemia and Ehrlich carcinoma cells. Ehrlich carcinoma assays with IC50 = 166 µM (1), 164 µM (2), 65 µM (6) and 10 µM (7) related to cell growth inhibitory effects were dose dependent. Furthermore, moderate cytotoxic activity against K562 leukemia cells was observed with IC50 = 38 µM (3), 33 µM (5), 36 µM (6) and 43 µM (7). The semi-synthetic 2, 6 and 7 showed similar results when compared to the corresponding natural clerodanes. O diterpeno clerodano trans-desidrocrotonina (1), constituinte majoritário de Croton cajucara, tem sua ocorrência correlacionada com o uso dessa planta na medicina popular. Investigações fitoquímicas levaram ao isolamento dos metabólitos 1, cajucarinolida (6), isocajucarinolida (7), trans-crotonina (2), trans-cajucarina B (3), cis-cajucarina B (4), trans-cajucarina A (5), N-metiltirosina, ácido vanílico e ácido 4-hidróxi-benzóico. 6 e 7 foram sintetizados em bons rendimentos através da oxidação de 1 com oxigênio-singlete. Todos os clerodanos foram ensaiados frente a células da leucemia humana K562 e do carcinoma de Ehrlich. Os efeitos inibitórios do crescimento celular foram dependentes da dose para os ensaios com o carcinoma de Ehrlich com IC50 = 166 µM (1), 164 µM (2), 65 µM (6) e 10 µM (7). Além disso, atividade citotóxica moderada foi observada contra as células da leucemia K562 com IC50 = 38 µM (3), 33 µM (5), 36 µM (6) e 43 µM (7). Os 6 e 7 semi-sintéticos mostraram resultados semelhantes quando comparados com os correspondentes clerodanos naturais. |
| Databáze: | OpenAIRE |
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