title: Cell specific cytotoxicity and structure-activity relationship of lipophilic 1-B-D-arabinofuranosylcytosine (ara-C) derivatives.
abstract: 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.
authors.affiliation: Dept. Oncology, University Hospital VU, Amsterdam.
authors.forename: G J
authors.initials: GJ
authors.lastname: Peters
authors.forename: D A
authors.initials: DA
authors.lastname: Voorn
authors.forename: C M
authors.initials: CM
authors.lastname: Kuiper
authors.forename: C L
authors.initials: CL
authors.lastname: van der Wilt
authors.forename: P
authors.initials: P
authors.lastname: Noordhuis
authors.forename: K
authors.initials: K
authors.lastname: Smid
authors.forename: F
authors.initials: F
authors.lastname: Myhren
authors.forename: M
authors.initials: M
authors.lastname: Sandvold
authors.forename: H R
authors.initials: HR
authors.lastname: Hendriks
mesh_terms: 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
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D003841:Deoxycytidine; D000093542:Gemcitabine