Department of Chemistry, Université de Montréal, PO Box 6128, Station Centre-Ville, Montréal, QC, H3C 3J7, Canada.
Department of Chemistry, Université de Montréal, PO Box 6128, Station Centre-Ville, Montréal, QC, H3C 3J7, Canada.
Eur J Med Chem. 2018 Nov 5;159:217-242. doi: 10.1016/j.ejmech.2018.09.043. Epub 2018 Sep 21.
A series of compounds containing pyrrolidine and pyrrolizidine cores with appended hydrophobic substituents were prepared as constrained analogs of FTY720 and phytosphingosine. The effect of these compounds on the viability of cancer cells, on downregulation of the nutrient transport systems, and on their ability to cause vacuolation was studied. An attempt to inhibit HDACs with some phosphate esters of our analogs was thwarted by our failure to reproduce the reported inhibitory action of FTY720-phosphate.
我们制备了一系列含有吡咯烷和吡咯里西啶核心并带有附加疏水取代基的化合物，作为 FTY720 和植物鞘氨醇的刚性类似物。研究了这些化合物对癌细胞活力、营养物质转运系统下调以及引起空泡化能力的影响。我们试图用我们的类似物的一些磷酸盐来抑制 HDAC，但未能重现 FTY720-磷酸盐的报道抑制作用，这使我们的尝试受挫。
