Antitumor activity of a novel orally effective nucleoside, 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine.
The antitumor activity of a novel 4'-thionucleoside, 1-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)cytosine (4'-thio-FAC), was evaluated. 4'-Thio-FAC inhibited the in vitro growth of various human cancer cell lines, particularly the growth of cell lines established from gastric and colorectal carcinomas, while its oxy-type congener 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)cytosine (FAC) showed little or no activity against such solid cancer cell lines. 4'-Thio-FAC showed a remarkable antitumor effect against human tumors subcutaneously implanted into nude mice and was highly effective even by oral administration. 4'-Thio-FAC was less susceptible to deamination by cytidine deaminase than FAC and 2'-deoxy-2',2'-difluorocytidine (gemcitabine) and therefore is a promising drug candidate for cancer chemotherapy.
Miura
S
S
Biochemicals Division, Yamasa Corporation, Chiba, Japan.
Yoshimura
Y
Y
Endo
M
M
Machida
H
H
Matsuda
A
A
Tanaka
M
M
Sasaki
T
T
D000284:Administration, Oral; D000586:Amination; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003564:Cytidine Deaminase / Q000378:metabolism; D005260:Female; D006801:Humans; D007941:Leukemia P388 / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
C114001:1-(2-deoxy-2-fluoro-4-thio-arabinofuranosyl)cytosine; D000970:Antineoplastic Agents; D003561:Cytarabine; D003564:Cytidine Deaminase