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1,2,3-Triazole-Substituted Oleanolic Acid Derivatives: Synthesis and Antiproliferative Activity
Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile
Facultad de Ciencias de la Salud, Universidad de Talca, Talca, Chile
* Author to whom correspondence should be addressed.
Received: 30 May 2013; in revised form: 26 June 2013 / Accepted: 27 June 2013 / Published: 1 July 2013
Abstract: Hybrid compounds are relevant products when searching for structure-activity relationships of natural products. Starting from the naturally occurring triterpene oleanolic acid, alkyl esters were prepared and treated with different aromatic azides using click chemistry to produce hybrid compounds. Some 18 new oleanolic acid derivatives were synthesized and the structures were confirmed by spectroscopic and spectrometric means. The antiproliferative activity of the new derivatives was evaluated towards normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), promyelocytic leukemia (HL-60), lung cancer (SK-MES-1) and bladder carcinoma (J82) cells. The alkyne esters 1 and 3 showed activity on all cell lines but without selectivity (19.6–23.1 μM and 14.1–56.2 μM, respectively), their respective methyl esters were inactive. Compounds with a benzene and p-anisole attached to the triazole ring, showed no antiproliferative effect. Introduction of a chlorine atom into the benzene ring (compound 9) elicited a selective effect against AGS cells (IC50 value: 8.9 μM). The activity was lost when the COOH function at C-28 was methylated. Better antiproliferative effect was found for compounds 11 and 15 bearing a p-toluenesulphonyl group, with values in the range of 10.8–47.1 μM and 11.5–22.2 μM, respectively. The effect, however, was not associated with selectivity.
Keywords: oleanolic acid; click chemistry; antiproliferative activity
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Pertino, M.W.; Lopez, C.; Theoduloz, C.; Schmeda-Hirschmann, G. 1,2,3-Triazole-Substituted Oleanolic Acid Derivatives: Synthesis and Antiproliferative Activity. Molecules 2013, 18, 7661-7674.
Pertino MW, Lopez C, Theoduloz C, Schmeda-Hirschmann G. 1,2,3-Triazole-Substituted Oleanolic Acid Derivatives: Synthesis and Antiproliferative Activity. Molecules. 2013; 18(7):7661-7674.
Pertino, Mariano W.; Lopez, Cecilia; Theoduloz, Cristina; Schmeda-Hirschmann, Guillermo. 2013. "1,2,3-Triazole-Substituted Oleanolic Acid Derivatives: Synthesis and Antiproliferative Activity." Molecules 18, no. 7: 7661-7674.