Cytotoxic mechanisms of new antitumor nucleoside analogues, 3'-ethynylcytidine (ECyd) and 3'-ethynyluridine (EUrd).

The cytotoxic mechanisms of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd) and 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil (EUrd) were studied with mouse mammary tumor FM3A cells and human fibrosarcoma HT1080 cells. ECyd and EUrd are converted to ECyd 5'-triphosphate (ECTP) in the cells. ECTP has also outstanding stability in the cells; the half life of ECTP in FM3A cells was more than 3 days. The metabolisms and mechanisms of these analogues may play a key role in a potent antitumor activities against slow-growing solid tumors.