SYNTHESIS OF PHOSPHOCHOLINE AND QUATERNARY AMINE ETHER LIPIDS AND EVALUATION OF IN-VITRO ANTINEOPLASTIC ACTIVITY

The in vitro antineoplastic activity of many phosphorus-containing (e. g., phosphocholines) and non-phosphorus-containing (e.g., quaternary a mmonium salts) ether lipids has been evaluated in the HL-60 promyelocy tic cell line. These compounds are analogues of ET-18-OMe ctadecyl-2-O -methyl-rac-glycero-3-phosphocholine). Structural modification of 1-(a lkylamido)-,-(alkylthio)-, and -(alkyloxy)propyl backbones has provide d further insight into the structure-activity relationships of these l ipids. In this study, along saturated C-1 chain and a three-carbon bac kbone with a single short C-2 substituent were preferred. At the posit ively charged nitrogen of phosphocholines, fewer than three substituen ts caused a significant loss of activity, and substituents larger than methyl decreased activity slightly. In the nonphosphorus compounds, m any nitrogen heterocycles and also a sulfonium moiety were incorporate d without changing the degree of activity; however, a thiazolium group decreased activity. The most active compound, 29 loxy)-2-methoxypropy l]-3-(hydroxymethyl)pyridinium bromide], was approximately twice as ac tive as the reference standard, ET-18-OMe, in a trypan blue dye exclus ion assay.