Lipidic peptides. XIII: Synthesis, structure elucidation and in vitro toxicity assessment of chlorambucil conjugates with lipidic acids, lipidic amino acids and their oligomers

Abstract A series of lipidic amides of chlorambucil 3a-c , oligomer 3d , lipidic esters of chlorambucil 5a-c and a chlorambucil conjugate containing both ester and amide linkage 7 were synthesized. The lipophilic character of the conjugates was altered by varying the number of lipidic acid units and the length of the alkyl chain. In vitro, the chlorambucil conjugates exhibited varying degrees of toxicity to ADJ/PC6 plasmacytoma cells. Their toxicity appeared to be related to their lipophilicity and the nature of the conjugating linkage.