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

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.

SUBMITTER: Garsi JB

PROVIDER: S-EPMC6217821 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Garsi Jean-Baptiste JB Sernissi Lorenzo L Vece Vito V Hanessian Stephen S McCracken Alison N AN Simitian Grigor G Edinger Aimee L AL

European journal of medicinal chemistry 20180921

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 ...[more]

PMID: 30292898

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