Cytotoxicity and pharmacokinetics of 1-beta-D-arabinofuranosyl-2-thiocytosine, a 2-sulphur substituted derivative of cytarabine.
1-(beta-D-Arabinofuranosyl)-2-thiocytosine (araSC), a 2-substituted derivative of cytarabine (araC), has been investigated for its cytotoxicity, enzymatic stability, plasma concentration-time profile in mice, and cytokinetics. This derivative showed strong cytotoxicity in several mammalian cell lines, although activity (IC50s) was weaker than araC. Greater stability to mouse cytidine deaminase was observed; the half-life in the presence of the enzyme was about 4-times longer than that of araC. The plasma concentration-time profile in mice in vivo showed prolonged retention of araSC when compared with araC. Cytokinetic study using flow cytometry indicated a non-S-phase specific effect of this compound.
Kawaguchi
T
T
Department of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
Ichikawa
T
T
Hasegawa
T
T
Saneyoshi
M
M
Yukita
A
A
Asano
M
M
Wakayama
T
T
Kato
H
H
Nagata
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001087:Arabinonucleosides / Q000493:pharmacokinetics* / Q000494:pharmacology*; D003564:Cytidine Deaminase / Q000378:metabolism; D003596:Cytosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000032:analysis; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007668:Kidney / Q000201:enzymology; D008297:Male; D051379:Mice; D014407:Tumor Cells, Cultured