Antitumor activity of a piperidine phospholipid

Arzneimittelforschung. 1994 Dec;44(12):1384-8.

Abstract

A piperidine phospholipid ((+/-)-2-[hydroxy] [1-octadecyloxycarbonylpiperidin-3-yl]methoxy-phosphinyl] oxy]-N,N,N, trimethylethaniminium hydroxide inner salt, SDZ 62-826) has been prepared that exhibited weak direct cytotoxicity and strong macrophage-induced cytotoxicity in vitro against a variety of murine and one human tumor cell lines. This compound was found to be as effective as ET-18-OCH3 and SRI 62-834, phospholipids with both strong direct and macrophage-induced cytotoxicity, in increasing survivors and reducing tumor volume when given either orally or intravenously in the mouse MethA fibrosarcoma model. These findings suggest that the macrophage-induced cytotoxicity exhibited by ET-18-OCH3 and other phospholipids may play an important role in this tumor model.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Binding, Competitive / drug effects
  • Cell Survival / drug effects
  • Fibroblasts / drug effects
  • Fibrosarcoma / drug therapy
  • Humans
  • Lethal Dose 50
  • Macrophages / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Phospholipid Ethers / chemical synthesis
  • Phospholipid Ethers / pharmacology*
  • Phospholipid Ethers / therapeutic use
  • Piperidines / chemical synthesis
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use
  • Platelet Activating Factor / metabolism
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Membrane Glycoproteins / drug effects
  • Receptors, Cell Surface*
  • Receptors, G-Protein-Coupled*
  • Receptors, Platelet-Derived Growth Factor / drug effects
  • Sarcoma, Experimental / drug therapy
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Phospholipid Ethers
  • Piperidines
  • Platelet Activating Factor
  • Platelet Aggregation Inhibitors
  • Platelet Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • SDZ 62-826
  • platelet activating factor receptor
  • Receptors, Platelet-Derived Growth Factor