title: Synthesis and antiproliferative activities of 5-azacytidine analogues in human leukemia cells.
abstract: Twenty-six 5-azacytidine analogues have been synthesized, including 4-amino- 6-alkyl-1-pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 1a-j, 6-amino-4-alkyl/aryl-1- pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 2a-f and 4-amino-6-alkyl-1,3,5-triazin-2- yl-1-thio-pyranosides/ribofuranosides 3a-j. The antiproliferative activities of these synthetic analogues were investigated in human leukemia HL-60 cells. Ribofuranosyl S-nucleoside 3a, a bioisostere of 5-azacytidine, had a similar antiproliferative ability as that of the latter. Introduction of a methyl at the 6 position of 5-azacytidine and/or replacement of the ribofuranosyl moiety with pyranosyl sugars or disaccharides significantly decreased the antiproliferative activities of the 5-azacytidine derivatives. Several compounds with the replacement of pyranosyl sugars enhanced all-trans retinoic acid-induced differentiation ability in human leukemia HL-60 cells.
authors: Shenyang Pharmaceutical University, Shenyang, 110016, PR China. guogang19761126@sina.com
authors: Gang
authors: G
authors: Guo
authors: Gang
authors: G
authors: Li
authors: Dan
authors: D
authors: Liu
authors: Qian-jiao
authors: QJ
authors: Yang
authors: Yu
authors: Y
authors: Liu
authors: Yong-kui
authors: YK
authors: Jing
authors: Lin-xiang
authors: LX
authors: Zhao
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D006131:Growth Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000964:Antimetabolites, Antineoplastic; D006131:Growth Inhibitors; D001374:Azacitidine