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A synthesis of a lipophilic derivative of methotrexate was devised, this being suitable for insertion into the membranes of carrier liposomes. The conjugate consisted of a rac-1,2-dioleoylglycerol residue attached via an ester bond to methotrexate via the b-alanyl-N-carbonylmethylene linker. A liposomal formulation of the derivative showed cytotoxic activity in cultures of M3 melanoma cells; this activity depended on the structure of the carbohydrate ligands on the liposome surface. As compared with a control liposome preparation carrying a diglyceride derivative of methotrexate and bearing an inactive pentaol aminoglucitol ligand, the cytotoxicity of liposomes carrying trisaccharide A residues was 1.5 times greater and that of liposome carrying tetrasaccharide sialyl-Lewis X was three times greater. 297 0091-150X/07/4106-0297

A series of N-acyl derivatives of 5-fluorouracil (5-FU) bearing residues of palmitic, p-myristoylaminobenzoic, p-oleoylaminobenzoic, and 1-adamantanecarbonic acids was synthesized. Relative rates of hydrolysis of derivatives mentioned under physiological conditions, at pH 7.2 and 37 degrees C, have shown that stability of these compounds increases with reducing of spatial accessibility of amide group at N1 in 5-FU. These substances incorporate easily into lipid bilayer; their liposomal preparations showed substantial cytostatic activity on HBL (human breast lymphoma) cells and are of interest as potential antitumor preparations. Also, a fluorescent analog, 1-[8-(3-perylenyl)octanoyl]-5-fluorouracil, destined for studies of the 5-FU derivatives behavior in cells and tissues was prepared.