Cytotoxicity and antileukaemic activity of new duplexes linking 3-C-ethynylcytidine and 5-fluorodeoxyuridine

The cytotoxic and antineoplastic potential of two new duplex drugs, ECyd-5-FdU and ECyd- lipid- 5-FdU, were compared with the activity of the parent single-nucleoside analogues, 3-C-ethynylcytidine (ECyd) and 5-fluorodeoxyuridine (5-FdU), either applied as monotherapy or simultaneously in equimolar concentrations simulating their ratio in a duplex drug. Murine leukaemia L1210 cells were used for comparative in vitro tests of the duplex and the single drugs. The tested substances were evaluated for their cytotoxicity, combinatory potential and revitalisation properties. Additionally, an in vivo model of leukaemia L1210-bearing mice of the DBA/2J strain was used for testing of acute toxicity and antileukaemic activity using various chemotherapeutic regimes. Based on the results of this study, the suitability of ECyd and 5-FdU for forming a duplex drug was discussed from the perspective of their expected synergistic anticancer activities. We found an improvement of chemotherapy outcomes of the new duplex drugs tested by comparing their in vitro cytotoxicity and an increase of the time of survival of experimental leukaemia-bearing mice in a statistically significant manner.