Synthesis and biological activities of 2'-deoxy-2'-fluoro-4'-thioarabinofuranosylpyrimidine and -purine nucleosides.
As part of our ongoing investigation of the synthesis of biologically interesting 2'-modified-4'-thionucleosides, we synthesized 2'-deoxy-2'-fluoro-4'-thioarabinofuranosylpyrimidine and -purine nucleosides, and evaluated their antiviral and antitumor activities. In the pyrimidine series, beta-anomers of 5-ethyluracil, 5-iodouracil, 5-chloroethyluracil, and 5-iodocytosine derivatives showed potent and selective anti-HSV-1 and HSV-2 activities in vitro. In the purine series, guanine and 2,6-diaminopurine derivatives showed prominent antiviral activities with slight cytotoxicity. On the other hand, the 5-fluorocytosine derivative (5F-4'-thioFAC) showed potent antitumor activity against both leukemia and solid tumor. Its antitumor spectrum against 14 human solid tumor and one leukemic cell lines was compared with that of 4'-thioFAC. The results showed that 5F-4'-thioFAC had an antitumor spectrum similar to that of 4'-thioFAC. However, 5F-4'-thioFAC was about 10 times less active than 4'-thioFAC.
Yoshimura
Y
Y
Biochemicals Division, Yamasa Corporation, Choshi, Chiba, Japan. yuyoshim@pharm.showa-u.ac.jp
Kitano
K
K
Yamada
K
K
Sakata
S
S
Miura
S
S
Ashida
N
N
Machida
H
H
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001087:Arabinonucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011684:Purine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013865:Thioglycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D001087:Arabinonucleosides; D011684:Purine Nucleosides; D011741:Pyrimidine Nucleosides; D013865:Thioglycosides