Natural and semi-synthetic clerodanes of Croton cajucara and their cytotoxic effects against ehrlich carcinoma and human K562 leukemia cells

• Published in: Journal of the Brazilian Chemical Society Vol. 18; no. 2; pp. 391 - 396
• Main Authors: Maciel, Maria Aparecida M., Martins, Jenilce R., Pinto, Angelo C., Kaiser, Carlos R., Esteves-Souza, Andressa, Echevarria, Aurea
• Format: Journal Article
• Language: English
• Published: Sociedade Brasileira de Química 01-04-2007
• Subjects: CHEMISTRY, MULTIDISCIPLINARY; trans-dehydrocrotonin; isocajucarinolide; cytotoxic activity; Croton cajucara; cajucarinolide
• ISSN: 0103-5053; 1678-4790
• DOI: 10.1590/S0103-50532007000200022

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.