Synthesis and Biological Evaluation of FTY720 (Fingolimod) Derivatives with Aromatic Head Group as Anticancer Agents

Chem Pharm Bull (Tokyo). 2018;66(10):1015-1018. doi: 10.1248/cpb.c18-00065.

Abstract

FTY720 is employed for the treatment of multiple sclerosis and exerts apoptotic effects on various cancers through protein phosphatase 2A (PP2A) activation. In compound 4, the dihydroxy head group of FTY720 was modified into dihydroxy phenyl group. The cell survival in compound 4 treated colorectal and gastric cancer cells was significantly reduced as compared with control, 34.6 and 25.1%, respectively. The docking study of compound 4 showed that the aromatic head group effectively binds to PP2A.

Keywords: FTY720; anticancer; derivative; fingolimod; sphingosine kinase.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Fingolimod Hydrochloride / chemical synthesis
  • Fingolimod Hydrochloride / chemistry
  • Fingolimod Hydrochloride / pharmacology*
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Fingolimod Hydrochloride