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.
Copyright © 2018 Elsevier Masson SAS. All rights reserved.
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cells, Cultured
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Epigenesis, Genetic / drug effects*
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Fingolimod Hydrochloride / analogs & derivatives
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Fingolimod Hydrochloride / chemistry
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Fingolimod Hydrochloride / pharmacology*
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Mice
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Molecular Structure
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Sphingosine / analogs & derivatives*
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Sphingosine / chemical synthesis
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Sphingosine / chemistry
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Sphingosine / pharmacology
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Fingolimod Hydrochloride
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phytosphingosine
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Sphingosine