TY - JOUR
T1 - Solvent-free synthesis of 6β-phenylamino-cholestan-3β,5α-diol and (25R)-6β-phenylaminospirostan-3β,5α-diol as potential antiproliferative agents
AU - Soto-Castro, Delia
AU - Lara Contreras, Roberto Carlos
AU - Pina-Canseco, María
AU - Santillán, Rosa
AU - Hernández-Huerta, María Teresa
AU - Negrón Silva, Guillermo E.
AU - Pérez-Campos, Eduardo
AU - Rincón, Susana
N1 - Publisher Copyright:
© 2017
PY - 2017
Y1 - 2017
N2 - 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 48 h 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.
AB - 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 48 h 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.
KW - Antiproliferative activity
KW - Cholesterol
KW - Diosgenin
KW - Sulfated zirconia
KW - β-Aminoalcohols
UR - http://www.scopus.com/inward/record.url?scp=85028347685&partnerID=8YFLogxK
U2 - 10.1016/j.steroids.2017.08.008
DO - 10.1016/j.steroids.2017.08.008
M3 - Artículo
C2 - 28827069
SN - 0039-128X
VL - 126
SP - 92
EP - 100
JO - Steroids
JF - Steroids
ER -