Arabinofuranosyl-5-azacytosine: antitumor and cytotoxic properties.

摘要: Arabinofuranosyl-5-azacytosine (ara-AC), a nucleoside combining the structural elements of 5-azacytidine and arabinofuranosylcytosine, exhibited unusually wide therapeutic activity against several murine leukemias all three human xenografts National Cancer Institute tumor panel. Activity was observed following either daily or an intermittent regimen treatment in i.p. L1210 model. However, when multiple doses were administered on each day, greater effect produced total dose reduced. Extensive necrosis by light electron microscopy P388 tumors treated with ara-AC. Following s.c. administration, ara-AC caused regression mammary lung (MX-1 LX-1) 93% inhibition colon (CX-1); other analogues this drug failed to demonstrate comparably broad spectrum activity. Morphological assessment revealed general loss cell-to-cell contact abundant 24 h after administration In culture, 50% inhibitory concentrations for cells at 1.9 4.5 microM, respectively, decline replication rates dependent concentration. The cytocidal nature demonstrated cloning experiments which it that abolished clonogenicity lymphoblasts but only minimally cytotoxic normal bone marrow progenitor cells. As adjudged flow cytometry, induced distinct slowing cell cycle traverse through S phase. Induction differentiation HL-60 culture another cytotropic drug. At 44% (10 microM ara-AC), cultured viable. Its antitumor activity, its selective toxicity cells, ability produce cytodifferentiation render interest as potential antineoplastic agent humans.