Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
Bioorg Med Chem Lett. 2012 Nov 1;22(21):6700-4. doi: 10.1016/j.bmcl.2012.08.093. Epub 2012 Sep 3.
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).
2-（β-D-呋喃核糖基）噻唑-4-甲酰胺（2）和两个具有 5-羟甲基-2-甲基-四氢呋喃[2,3-d][1,3]二恶烷-6-醇部分作为糖类似物的噻唑呋喃类似物（27 和 28）已被合成并评估其对一组人类肿瘤细胞系（K562、HL60、Jurkat、Raji 和 HeLa）的体外抗肿瘤活性。与之前的文献报道相反，代谢 MTT 测定法显示出 2 对 K562（IC50=0.15 μM）和 HL-60（IC50=0.13 μM）细胞的显著细胞毒性。流式细胞术数据表明，类似物 2 在 K562 细胞培养物中的细胞毒性作用可能是通过细胞凋亡介导的，与噻唑呋喃相反，噻唑呋喃在 24 小时后不会诱导 K562 细胞凋亡，这表明其作用机制不同。类似物 2、27 和 28 对 Jurkat、Raji 和 HeLa 细胞也具有活性，IC50 值在 0.06 至 5.61 μM 范围内，但对正常胎儿肺成纤维细胞（MRC-5）完全没有活性。
