Sapogeninas de cáscaras de chenopodium quinoa, obtención de sus derivados, y evaluación de su actividad citotóxica
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Rev. Bol. Quim
Abstract
En este trabajo, presentamos la evaluación de dos tipos de métodos para la obtención sapogeninas por hidrólisis acida de un extracto hidroalcohólico rico en saponinas de cáscaras de quinua. En el primer método, denominado método de microondas, la solución ácida de saponinas se agitó previamente durante un minuto en un microondas y luego se calentó y agitó a 100 °C durante 15 minutos. En el segundo, llamado método convencional, la misma solución ácida se calentó y agitó a 80°C durante 4 h, nuestros resultados mostraron que el método convencional es mejor para obtener más cantidad de sapogeninas. Luego aislamos cuatro sapogeninas ácido oleanólico (1), metiloleanato (2), hederagenina (3) y ácido fitolaccagénico (4) evaluando su actividad citotóxica en células humanas de cáncer de mama JIMT-1 y células epiteliales de mama MCF-10A similares a células humanas normales, observando que todos ellos tienen citotoxicidad en ambas líneas celulares, pero el compuesto más activo es la hederagenina, que es más tóxica en las células JIMT-1 (IC50 27.3 µM) que en las células MCF-10A (IC50 39.6 µM). Finalmente, obtuvimos cuatro nuevos derivados de ácido oleanólico, la principal sapogenina aislada, por oxidación del grupo OH en C-3 a carbonilo (5) y reacción subsiguiente de condensación aldólica, añadiendo al carbono C-2 los siguientes aldehidos: benzaldehído 6a, p-metilbenzaldehído 6b, m-metilbenzaldehído 6c, y o-metilbenzaldehído 6d, estas síntesis se llevaron a cabo para incorporar un aceptor de Michael en la estructura molecular para potenciar la actividad biológica, obtuvimos rendimientos de alrededor del 50% para 6a y 6b y de alrededor del 10% para 6c y 6d.
In this paper, we present the evaluation of two types of methods for obtaining sapogenins by acid hydrolysis of a hydroalcoholic extract rich in saponins from quinoa husks. In the first method, called microwave method, the acid solution of saponins was pre-stirred for one minute in a microwave and then was heated and stirred at 100 °C for 15 min. In the second one, called conventional method, the same acid solution was heated and stirred at 80 °C for 4 h. The results show that the conventional method is better to obtain more quantity of sapogenins. Then four sapogenins were isolated: oleanolic acid (1), methyl oleanate (2), hederagenin (3), and phytolaccagenic acid (4). The cytotoxicity of the compounds was evaluated in human JIMT-1 breast cáncer cells and human MCF-10A normal-like breast epithelial cells. The most active compound is hederagenin, which is more toxic in JIMT-1 cells (IC50 27.3 µM) than in MCF-10A cells (IC50 39.6 µM). Methyl oleanate is somewhat less toxic than hederagenin while oleanolic acid and phytolaccagenic acid needed treatment concentrations up to 100 uM to become cytotoxic. Finally, we obtained four new derivatives of oleanolic acid, the major sapogenin isolated, by oxidation of the OH group in C-3 to carbonyl (5) and subsequent reaction of aldol condensation, adding to carbon C-2 the follow aldehydes: benzaldehyde 6a, p- methylbenzaldehyde 6b, m-methylbenzaldehyde 6c, and o-methylbenzaldehyde 6d, these synthesis were carried out in order to incorporate a Michael-acceptor into a molecular structure to enhance the biological activity, we obtained yields of around 50% for 6a and 6b, and of around 10% for 6c and 6d.
In this paper, we present the evaluation of two types of methods for obtaining sapogenins by acid hydrolysis of a hydroalcoholic extract rich in saponins from quinoa husks. In the first method, called microwave method, the acid solution of saponins was pre-stirred for one minute in a microwave and then was heated and stirred at 100 °C for 15 min. In the second one, called conventional method, the same acid solution was heated and stirred at 80 °C for 4 h. The results show that the conventional method is better to obtain more quantity of sapogenins. Then four sapogenins were isolated: oleanolic acid (1), methyl oleanate (2), hederagenin (3), and phytolaccagenic acid (4). The cytotoxicity of the compounds was evaluated in human JIMT-1 breast cáncer cells and human MCF-10A normal-like breast epithelial cells. The most active compound is hederagenin, which is more toxic in JIMT-1 cells (IC50 27.3 µM) than in MCF-10A cells (IC50 39.6 µM). Methyl oleanate is somewhat less toxic than hederagenin while oleanolic acid and phytolaccagenic acid needed treatment concentrations up to 100 uM to become cytotoxic. Finally, we obtained four new derivatives of oleanolic acid, the major sapogenin isolated, by oxidation of the OH group in C-3 to carbonyl (5) and subsequent reaction of aldol condensation, adding to carbon C-2 the follow aldehydes: benzaldehyde 6a, p- methylbenzaldehyde 6b, m-methylbenzaldehyde 6c, and o-methylbenzaldehyde 6d, these synthesis were carried out in order to incorporate a Michael-acceptor into a molecular structure to enhance the biological activity, we obtained yields of around 50% for 6a and 6b, and of around 10% for 6c and 6d.
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Vol. 35, No. 3