Induction of differentiation of human myeloid leukemia HL‐60 cells by novel nonphosphorus alkyl ether lipids

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Abstract
We synthesized a new series of nonphosphorus alkyl ether glycerolipids, in which the 2-acetyl group of platelet-activating factor was replaced by a pyrimidin-2-yl group and the 3-phosphocholine portion by anω-(substituted ammonio)ethoxyethyl side-chain including ω-thiazolio-, imidazolio-and pyridinio groups with or without a carboxyl substituent, respectively (compound I–XI). Their effects on cell proliferation and differentiation of human myeloid leukemia HL-60 cells were examined. Incubation of HL-60 cells with these cationic and zwitterionic alkyl ether lipids inhibited proliferation of HL-60 cells with IC50 values ranging from 10 to 500 ng/mL. The cells were induced by the lipids to differentiate into morphologically and functionally mature granulocytes. Among the compounds we tested, 1-octadecyl-2-pyrimidinyl-3-[3-(5-carboxylatepenty)imidazolioethoxyethyl]glycerol (compound I) was the most effective in inducing differentiation of HL-60 cells. Compound I showed on a molar basis, an inhibitory effect on the leukemic cells over 50 times greater than did 2-(2-dodecyloxyethoxy)ethyl 2-pyridinioethyl phosphate, the antileukemic alkyl ether phospholipid.