title: Nucleoside conjugates. 10. Synthesis and antitumor activity of 1-beta-D-arabinofuranosylcytosine 5'-diphosphate-1,2-dipalmitins.
abstract: Three 1-beta-D-arabinofuranosylcytosine 5'-diphosphate-1,2-dipalmitins from L-, D-, and DL-alpha-dipalmitoylphosphatidic acids have been synthesized and their antitumor activity against two ara-C2 resistant L1210 lymphoid leukemia sublines in mice were evaluated. These new prodrugs of ara-C include ara-CDP-L-dipalmitin, ara-CDP-D-dipalmitin, and ara-CDP-DL-dipalmitin. The L and DL isomers produced significant increase in life span (greater than 400%) and four to five long-term survivors (greater than 45 days) out of six animals bearing ip implanted partially ara-C resistant L1210 subline [L1210/ara-C (I)], while the D isomer displayed a marginal activity (ILS 100-121%). In contrast, the L isomer was completely ineffective against deoxycytidine kinase deficient ara-C resistant L1210 subline [L1210/ara-C (II)]. However, the results demonstrate that the L and DL isomers of ara-CDP-dipalmitin are promising new prodrugs of ara-C with improved efficacy.
authors.affiliation: Department of Neurosurgery, Roswell Park Memorial Institute, Buffalo, New York 14263.
authors.forename: C I
authors.initials: CI
authors.lastname: Hong
authors.forename: S H
authors.initials: SH
authors.lastname: An
authors.forename: L
authors.initials: L
authors.lastname: Schliselfeld
authors.forename: D J
authors.initials: DJ
authors.lastname: Buchheit
authors.forename: A
authors.initials: A
authors.lastname: Nechaev
authors.forename: A J
authors.initials: AJ
authors.lastname: Kirisits
authors.forename: C R
authors.initials: CR
authors.lastname: West
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D055598:Chemical Phenomena; D002621:Chemistry; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D004351:Drug Resistance; D004358:Drug Therapy; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D008811:Mice, Inbred DBA; D011355:Prodrugs / Q000138:chemical synthesis / Q000627:therapeutic use*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D003561:Cytarabine; C018457:1 beta-D-arabinofuranosylcytosine 5'-diphosphate-L-1,2 dipalmitin