IN-VITRO ANTILEUKEMIC ACTIVITY AND CHEMICAL TRANSFORMATION OF THE 5'-CHLORO-5'-DEOXY DERIVATIVE OF CYCLOCYTIDINE

Hydrochloride of 5'-chloro-5'-deoxy-cyclocytidine (Cl-cC) is an analog ue of cyclocytine hydrochloride (cC), a prodrug of the compound with t he strong antileukemic activity arabinosylcytosine (araC). This paper is devoted to the study of its cytotoxic activity in vitro and to the effect of acid and alkaline conditions and temperature on its stabilit y. Cl-cC inhibits not only the growth of L1210 leukemia cells in vitro and the DNA synthesis (IC50 = 0.09 mu mol/l) but, at the same time, i t has a weak effect on RNA synthesis IC50 > 250 mu mol/l) and no effec t on proteosynthesis. In alkaline conditions Cl-cC is transformed to 5 '-chloro-araC and 2',5'-anhydro-araC but is more stable in acid soluti ons.