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 inter esting 2'-modified-4'-thionucleosides, we synthesized 2'-deoxy-2'-fluoro-4' -thioarabinofuranosylpyrimidine and -purine nucleosides, and evaluated thei r antiviral and antitumor activities. In the pyrimidine series, beta-anomer s of 5-ethyluracil, 5-iodouracil, 5-chloroethyluracil, and 5-iodocytosine d erivatives showed potent and selective anti-HSV-1 and HSV-2 activities in v itro. In the purine series, guanine and 2,6-diaminopurine derivatives showe d prominent antiviral activities with slight cytotoxicity. On the other han d, the 5-fluorocytosine derivative (5F-4'-thioFAC) showed potent antitumor activity against both leukemia and solid tumor. Its antitumor spectrum agai nst 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 spec trum similar to that of 4'-thioFAC. However, 5F-4'-thioFAC was about 10 tim es less active than 4'-thioFAC. (C) 2000 Elsevier Science Ltd. All rights r eserved.