Antiproliferative activity and mechanism of action of fatty acid derivatives of arabinosylcytosine (ara-C) in leukemia and solid tumor cell lines.
Resistance to, the hydrophilic drug ara-C, might be meditated by decreased membrane transport. Lipophilic prodrugs were synthesized to facilitate uptake. These compounds were equally active as ara-C, while the compounds with the shortest fatty-acid group and highest number of double bonds were the more active. These compounds also show a better retention profile, their effect is retained longer than for ara-C.
Bergman
A M
AM
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Kuiper
C M
CM
Myhren
F
F
Sandvold
M L
ML
Hendriks
H R
HR
Peters
G J
GJ
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D051381:Rats; D013997:Time Factors; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D005227:Fatty Acids; D003561:Cytarabine; D003841:Deoxycytidine; D000093542:Gemcitabine