Antitumor activity of a novel orally effective nucleoside, 1-(2-deoxy-2-fluoro-4-thio-β-d-arabinofuranosyl)cytosine

The antitumor activity of a novel 4′-thionucleoside, 1-(2-deoxy-2-fluoro-4-thio-β-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-β-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.