Cyclic oxygen analogues of alkyl-lysophospholipids. Synthesis and neoplastic cell growth inhibitory properties.
Ether phospholipids have demonstrated both in vitro and in vivo activity against a wide variety of tumor cell lines. The known cyclic ether phospholipid, SRI 62-834, was used as the model to prepare eight novel phospholipids containing a cyclic ether. All of the compounds were as effective as ET-18-OCH3 in their ability to activate macrophage-induced cytotoxicity against the Abelson-8.1 tumor cell line but varied in their direct cytotoxic effects. One of the new compounds, SDZ 62-406, was selected for in vivo studies and showed oral and i.v. activity in the mouse MethA fibrosarcoma model in the same range as ET-18-OCH3. No correlation was found between the direct or macrophage-activated cytotoxicity and the ability of the compounds to inhibit or promote platelet-activating factor (PAF)-induced aggregation of human platelets.
Houlihan
W J
WJ
Sandoz Research Institute, East Hanover, NJ 07936.
Lee
M L
ML
Munder
P G
PG
Winslow
C M
CM
Cheon
S H
SH
D'Aries
F J
FJ
DeLillo
A K
AK
Jaeggi
C S
CS
Mason
R B
RB
Parrino
V A
VA
D000818:Animals; D000970:Antineoplastic Agents; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D010742:Phospholipid Ethers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D012513:Sarcoma, Experimental / Q000188:drug therapy; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; C072627:SDZ 62-406; C026659:edelfosine