title: Synthesis of novel nucleoside analogue phosphorothioamidate prodrugs and in vitro anticancer evaluation against RKO human colon carcinoma cells.
abstract: Novel phosphorothioamidates of pyrimidine nucleoside analogues have been prepared and evaluated in vitro against RKO human colon cancer cell by the MTT cytotoxicity assay. The parent nucleoside analogues were inactive in this assay, while the phosphorothioamidate prodrugs were active at low uM levels in some cases. The O-isopropyl phosphorothioamidate of 2 ',3 '-O-isopropylidene-uridine containing the L-phenylalanine ethyl ester 6f was the most active at 148 uM, a 10-fold enhancement in anticancer activity compared with the parent nucleoside 2 with no increase in cytotoxicity.
authors.affiliation: College of Sciences, Tianjin University of Science and Technology, Tianjin, China. liuwei2006@tust.edu.cn
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Honggang
authors.initials: H
authors.lastname: Zhou
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Miao
authors.forename: Yufen
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D006801:Humans; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010756:Phosphoric Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D009705:Nucleosides; D009946:Organothiophosphorus Compounds; D010756:Phosphoric Acids; D011355:Prodrugs; C011067:phosphoramidic acid