title: Design, synthesis, and in vitro anti-hepatocellular carcinoma of novel thymine thioglycoside analogs as new antimetabolic agents.
abstract: A first reported direct method for preparation of thymine thioglycoside analogs utilizing novel pyrimidine-2(1H)-thiones and α-bromoglucose or α-bromogalactose tetraacetate as starting components is described. The synthetic potential of the method is demonstrated. The evaluation of antiproliferative activity against HepG-2 cell lines (Liver carcinoma cell lines) shows that most of the compounds have high antitumor activities especially 6b, 6e, 11b, and 12b. Moreover, molecular modelings of these compounds reveal that they have high binding affinity through hydrogen bond interaction with the binding pocket of thymidylate synthase dihydrofolate reductase (TS-DHFR).
authors.affiliation: a Chemistry Department, Faculty of Science , Helwan University , Helwan , Cairo , Egypt.
authors.forename: Galal H
authors.initials: GH
authors.lastname: Elgemeie
authors.affiliation: b Pharmaceutical Chemistry Department, Faculty of Pharmacy , Ahram Canadian University, Giza , Egypt.
authors.forename: Ayman B
authors.initials: AB
authors.lastname: Farag
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D013865:Thioglycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013940:Thymidylate Synthase / Q000378:metabolism; D013941:Thymine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009097:Multienzyme Complexes; D013865:Thioglycosides; C056930:thymidylate synthase-dihydrofolate reductase; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase; D013941:Thymine
keywords: Thymine thioglycoside; in vitro anticancer activity; pyrimidine 2(1H)-thiones; α-bromoglucose