Evaluation of the antitumor activity of 1-(3-C-ethynyl-beta-D-ribofuranosyl) (PJ272), a recent ribonucleoside analogue

The antiproliferative proper ties of a new ribonucleoside derivative, 1-(3' -C-ethynyl-beta-D-ribofuranosyl) uracil (PJ 272) that we synthesized a few years ago, were investigated in vitro on a variety of tumor cell lines from human and murine origins and in vivo, in tumor bearing mice. Using the 3(4 ,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, we s howed the ability of this compound to depress, at nanomolar concentrations, the growth of leukemia and lymphoma cultured cells. In 7 out of 8 tumor ce ll lines tested concentration of 50% inhibition (IC50) was found to be less than 25 nM. PJ 272 was also shown to present the same cytotoxicity against K562 Adriamycin-resistant cell line, which express a multi-drug resistance (MDR) phenotype, and its Adriamycin-sensitive parent cell fine. Moreover; when injected intraperitoneally at 20 mg/kg every three days, PJ 272 was fo und to significantly increase the survival rate (T/C=149%) of DBA/2 mice in jected intraperitoneally with L1210 leukemic cells. Taken together; these r esults suggest that PJ 272 could be considered as a potentially very active drug against lymphoma and leukemia.