Solvent-free synthesis of 6 beta-phenylamino-cholestan-3 beta,5 alpha-diol and (25R)-6 beta-phenylaminospirostan-3 beta,5 alpha-diol as potential antiproliferative agents

摘要

In this paper is described a synthetic route to 6 beta-phenylamino-cholestan-3 beta,5 alpha-diol and (25R)-613-phenylaminospirostan-3 beta,5 alpha-diol, starting from cholesterol and diosgenin, respectively. The products were obtained in two steps by epoxidation followed by aminolysis, through an environmentally friendly and solvent-free method mediated by SZ (sulfated zirconia) as catalyst. The use of SZ allows chemo- and regioselective ring opening of the 5,6 alpha-epoxide during the aminolysis reaction eliminating the required separation of the epoxide mixture. The products obtained were spectroscopically characterized by H-1, PENDANT C-13 NMR and HETCOR experiments, and complemented with FTIR-ATR and HRMS. The antiproliferative effect of the beta-aminoalcohols was evaluated on MCF-7 cells after 48 h of incubation, by MIT and CVS assays. These methodologies showed that both compounds have antiproliferative activity, being more active the cholesterol analogue. Additionally, the cell images obtained by Harris' Hematoxylin and Eosin (H & E) staining protocol, evidenced formation of apoptotic bodies due to the presence of the obtained beta-aminoalcohols in a dose-dependent manner.