Cell specific cytotoxicity and structure-activity relationship of lipophilic 1-b-d-arabinofuranosylcytosine (ara-C) derivatives

Lipophilic derivatives of ara-C were developed with the aim to improve drug penetration and retention in solid tumors. Ara-C was esterified at the 5'- position with fatty acids (16-22 C-atoms, 0-3 double bonds). The derivative s were inactive in cell lines with various forms of ara-C and 2',2'-difluor odeoxycytidine (dFdC, gemcitabine) resistance, including deoxycytidine kina se (dCK) deficiency. The activity in the parent cell lines correlated negat ively with chain length and positively with double bonds.