Synthesis and evaluation of fatty acyl ester derivatives of cytarabine as anti-leukemia agents.
Cytarabine is a chemotherapeutic agent predominately used for the treatment of acute myeloid leukemia and lymphoblastic leukemia. Cytarabine is a polar nucleoside, has a short plasma half-life, and its use is associated with severe side effects. Fatty acyl derivatives of cytarabine were synthesized with the expectation to improve cellular uptake and generate derivatives with a longer duration of action. Multi-step protection and deprotection reactions of hydroxyl and amino groups and conjugation with a fatty acid (i.e., myristic acid and 12-thioethyldodecanoic acid) afforded 5'-O-substituted, 2'-O-substituted, and 2',5'-disubstituted fatty acyl derivatives of cytarabine. 2',5'-Dimyristoyl derivative of cytarabine was found to inhibit the growth of CCRF-CEM cells by approximately 76% at concentration of 1 microM after 96 h incubation.
Chhikara
Bhupender S
BS
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 41 Lower College Road, Kingston, RI 02881, USA.
Mandal
Deendayal
D
Parang
Keykavous
K
D000964:Antimetabolites, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004952:Esters / Q000737:chemistry / Q000494:pharmacology; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D004952:Esters; D005227:Fatty Acids; D011355:Prodrugs; D003561:Cytarabine