Antitumor activity of a piperidine phospholipid.
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.
Houlihan
W J
WJ
Sandoz Research Institute, East Hanover, New Jersey.
Lee
M L
ML
Munder
P G
PG
Handley
D A
DA
Nemecek
G A
GA
Jaeggi
C S
CS
Winslow
C W
CW
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D001667:Binding, Competitive / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D005354:Fibrosarcoma / Q000188:drug therapy; D006801:Humans; D007928:Lethal Dose 50; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010742:Phospholipid Ethers / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D010972:Platelet Activating Factor / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects; D012513:Sarcoma, Experimental / Q000188:drug therapy; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; D010880:Piperidines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C091903:SDZ 62-826; C039351:platelet activating factor receptor; D017479:Receptors, Platelet-Derived Growth Factor