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

• Published in: Steroids 2017-10, Vol.126, p.92-100
• Main Authors: Soto-Castro, Delia, Lara Contreras, Roberto Carlos, Pina-Canseco, Maria del Socorro, Santillán, Rosa, Hernández-Huerta, María Teresa, Negrón Silva, Guillermo E., Pérez-Campos, Eduardo, Rincón, Susana
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative activity; Apoptosis - drug effects; Cell Proliferation - drug effects; Chemistry Techniques, Synthetic; Cholestanols - chemical synthesis; Cholestanols - chemistry; Cholestanols - pharmacology; Cholesterol; Diosgenin; Humans; MCF-7 Cells; Sulfated zirconia; β-Aminoalcohols
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2017.08.008

[Display omitted] •Efficient route to steroidal β-aminoalcohols from diosgenin and cholesterol.•Solvent free chemoselective aminolysis of steroidal epoxides using sulfated zirconia as catalyst.•Antiproliferative activity shows that the cholesterol analog is more active. In this paper is described a synthetic route to 6β-phenylamino-cholestan-3β,5α-diol and (25R)-6β-phenylaminospirostan-3β,5α-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 5,6α-epoxide during the aminolysis reaction eliminating the required separation of the epoxide mixture. The products obtained were spectroscopically characterized by 1H, PENDANT 13C NMR and HETCOR experiments, and complemented with FTIR-ATR and HRMS. The antiproliferative effect of the β-aminoalcohols was evaluated on MCF-7 cells after 48h of incubation, by MTT 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 β-aminoalcohols in a dose-dependent manner.