title: Synthesis and in vitro antitumour screening of 2-(β-D-xylofuranosyl)thiazole-4-carboxamide and two novel tiazofurin analogues with substituted tetrahydrofurodioxol moiety as a sugar mimic.
abstract: 2-(β-D-xylofuranosyl)thiazole-4-carboxamide (2) and two new tiazofurin analogues with 5-hydroxymethyl-2-methyl-tetrahydro-furo[2,3-d][1,3]dioxol-6-ol moiety as a sugar mimic (27 and 28) have been synthesized and evaluated for their in vitro antitumour activity against a panel of human tumour cell lines (K562, HL 60, Jurkat, Raji and HeLa). In contrast to previous literature reports, a metabolic MTT assay revealed remarkable cytotoxicity of 2 against K562 (IC(50)=0.15 μM) and HL-60 (IC(50)=0.13 μM) cells. Flow cytometry data suggest that cytotoxic effects of analogue 2 in the culture of K562 cells might be mediated by apoptosis, in opposite to tiazofurin, which did not induce apoptosis of K562 cells after 24h, thus suggesting a different mechanism of action. All three analogues 2, 27 and 28 were also active against Jurkat, Raji and HeLa cells, with IC(50) values in the range from 0.06 to 5.61 μM, but were completely inactive against the normal foetal lung fibroblasts (MRC-5).
authors.affiliation: Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia. mirjana.popsavin@dh.uns.ac.rs
authors.forename: Mirjana
authors.initials: M
authors.lastname: Popsavin
authors.forename: Saša
authors.initials: S
authors.lastname: Spaić
authors.forename: Miloš
authors.initials: M
authors.lastname: Svirčev
authors.forename: Vesna
authors.initials: V
authors.lastname: Kojić
authors.forename: Gordana
authors.initials: G
authors.lastname: Bogdanović
authors.forename: Velimir
authors.initials: V
authors.lastname: Popsavin
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D018716:Molecular Mimicry; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014994:Xylose / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002241:Carbohydrates; D009705:Nucleosides; D013844:Thiazoles; D012254:Ribavirin; C071387:2-beta-xylofuranosylthiazole-4-carboxamide; D014994:Xylose; C033706:tiazofurin