2. Academic Validation
  3. In search of constrained FTY720 and phytosphingosine analogs as dual acting anticancer agents targeting metabolic and epigenetic pathways

In search of constrained FTY720 and phytosphingosine analogs as dual acting anticancer agents targeting metabolic and epigenetic pathways

  • Eur J Med Chem. 2018 Nov 5:159:217-242. doi: 10.1016/j.ejmech.2018.09.043.
Jean-Baptiste Garsi 1,  Lorenzo Sernissi 1,  Vito Vece 1,  Stephen Hanessian 2,  Alison N McCracken 3,  Grigor Simitian 3,  Aimee L Edinger 4
Affiliations

Affiliations

  • 1 Department of Chemistry, Université de Montréal, PO Box 6128, Station Centre-Ville, Montréal, QC, H3C 3J7, Canada.
  • 2 Department of Chemistry, Université de Montréal, PO Box 6128, Station Centre-Ville, Montréal, QC, H3C 3J7, Canada. Electronic address: stephen.hanessian@umontreal.ca.
  • 3 Department of Developmental and Cell Biology, University of California, Irvine, 2128 Natural Sciences 1, CA, 92697-2300, USA.
  • 4 Department of Developmental and Cell Biology, University of California, Irvine, 2128 Natural Sciences 1, CA, 92697-2300, USA. Electronic address: aedinger@uci.edu.
PMID: 30292898 DOI: 10.1016/j.ejmech.2018.09.043
Abstract

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.

Keywords

Cytotoxicity; Nutrient transporter; Protein phosphatase 2A; Ring-constrained sphingosines; Vacuolation.

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