Effect and mode of action of N4-behenoyl-beta-D-arabinofuranosylcytosine.

N4-Behenoyl-beta-D-arabinofuranosylcytosine (behenoyl ara-C, NSC 239336) enhanced chemotherapeutic activity against L1210 murine leukemia as compared with 1-beta-D-arabinofuranosylcytosine (ara-C). Behenoyl ara-C was resistant to deamination by cytidine deaminase, which was supposed to be liable for inactivating ara-C in vivo. Behenoyl ara-C exerted chemotherapeutic activity when administered before implantation of leukemic cells, suggesting prolonged circulation in the body fluid. These two findings indicate that the resistance to the enzymatic deamination and hydrophobicity endowed by behenic residue were responsible for the enhanced chemotherapeutic activity of behenoyl ara-C. This idea was supported by the finding that ara-C encapsulated in liposome enhanced chemotherapeutic activity.