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 derivatives were inactive in cell lines with various forms of ara-C and 2',2'-difluorodeoxycytidine (dFdC, gemcitabine) resistance, including deoxycytidine kinase (dCK) deficiency. The activity in the parent cell lines correlated negatively with chain length and positively with double bonds.
Peters
G J
GJ
Dept. Oncology, University Hospital VU, Amsterdam.
Voorn
D A
DA
Kuiper
C M
CM
van der Wilt
C L
CL
Noordhuis
P
P
Smid
K
K
Myhren
F
F
Sandvold
M
M
Hendriks
H R
HR
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D003841:Deoxycytidine; D000093542:Gemcitabine