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