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 analogue of cyclocytine hydrochloride (cC), a prodrug of the compound with the 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 stability. Cl-cC inhibits not only the growth of L1210 leukemia cells in vitro and the DNA synthesis (IC50 = 0.09 mumol/l) but, at the same time, it has a weak effect on RNA synthesis (IC50 > 250 mumol/l) and no effect on proteosynthesis. In alkaline conditions Cl-cC is transformed to 5'-chloro-araC and 2',5'-anhydro-araC but is more stable in acid solutions.
Stankovicová
M
M
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.
Rauko
P
P
Bachratá
M
M
Blesová
M
M
Sveda
P
P
D003504:Ancitabine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004355:Drug Stability; D007938:Leukemia / Q000188:drug therapy*; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D012313:RNA; D004247:DNA; D003504:Ancitabine