Synthesis and biological evaluation of analogs of AAL(S) for use as ceramide synthase 1 inhibitors

Org Biomol Chem. 2015 Dec 28;13(48):11593-6. doi: 10.1039/c5ob01931a. Epub 2015 Nov 4.

Abstract

A convergent synthesis to access hydrophobic tail analogs and head group modifications of AAL(S) is described. The analogs synthesised were evaluated for their ability to inhibit ceramide synthase 1 and for their cytotoxicity in K562 cells. Our results have identified inhibitors which are non-cytotoxic yet maintain CerS1 inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Alcohols / chemical synthesis*
  • Amino Alcohols / chemistry
  • Amino Alcohols / pharmacology
  • Cell Survival / drug effects
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Fingolimod Hydrochloride / chemical synthesis*
  • Fingolimod Hydrochloride / chemistry
  • Fingolimod Hydrochloride / pharmacology
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • K562 Cells
  • Models, Biological
  • Molecular Structure
  • Oxidoreductases / antagonists & inhibitors*

Substances

  • AAL(S) compound
  • Amino Alcohols
  • Enzyme Inhibitors
  • Oxidoreductases
  • dihydroceramide desaturase
  • Fingolimod Hydrochloride