Synthesis and biological activities of 2′-deoxy-2′-fluoro-4′-thioarabinofuranosylpyrimidine and -purine nucleosides

Abstract

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, β-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.