Synthesis of the spin-labeled derivative of an ether-linked phospholipid possessing high antineoplastic activity.
We report here the complete synthesis of the spin-labeled derivative of an antitumor ether phospholipid, 1-O-octadecyl-2-O-(4'-doxylpentyl)-rac-glycerol-3-phosphocholine. This also represents the first time that the synthesis of a nitroxide spin-labeled diether phospholipid is described. In vitro experiments showed that at micromolar concentrations, this new analog is readily incorporated into the plasma membranes of human HL60 and mouse E8/AK.D1 leukemic cells, and subsequently kills the cells. The availability of this new probe should permit the electron spin resonance spectroscopic approach to investigate ways by which anti-tumor ether phospholipids selectively destroy the tumor cells.
Joseph
J
J
Department of Radiology, Medical College of Wisconsin, Milwaukee 53226.
Shih
C C
CC
Lai
C S
CS
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000473:pathology; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D010742:Phospholipid Ethers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013113:Spin Labels / Q000138:chemical synthesis*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; D013113:Spin Labels; C026659:edelfosine