Way Hannah, Roh Joshua, Venteicher Brooklynn, Chandra Surabhi, Thomas Allen A
Department of Chemistry, University of Nebraska at Kearney, Kearney, Nebraska, USA.
Department of Biology, University of Nebraska at Kearney, Kearney, Nebraska, USA.
Nucleosides Nucleotides Nucleic Acids. 2023;42(1):38-64. doi: 10.1080/15257770.2022.2107218. Epub 2022 Aug 5.
We report the synthesis and cytotoxicity in MCF-7 and MDA-MB-231 breast cancer cells of novel 1,2,3- and 1,2,4-triazolyl analogs of ribavirin. We modified ribavirin's carboxamide moiety to test the effects of lipophilic groups. 1-β-D-Ribofuranosyl-1-1,2,3-triazoles were prepared using Click Chemistry, whereas an unprecedented application of a prior 1,2,4-triazole ring synthesis was used for 1-β-D-ribofuranosyl-1-1,2,4-triazole analogs. Though cytotoxicity was mediocre and there was no correlation with lipophilicity, we discovered that a structurally similar concentrative nucleoside transporter 2 (CNT2) inhibitor was modestly cytotoxic (MCF-7 IC of 42 µM). These syntheses could be used to efficiently investigate variation in the nucleobase.
我们报告了新型利巴韦林的1,2,3 - 和1,2,4 - 三唑基类似物在MCF - 7和MDA - MB - 231乳腺癌细胞中的合成及细胞毒性。我们对利巴韦林的羧酰胺部分进行修饰以测试亲脂性基团的作用。利用点击化学制备了1-β-D-呋喃核糖基-1,2,3 - 三唑，而1-β-D-呋喃核糖基-1,2,4 - 三唑类似物则采用了前所未有的先合成1,2,4 - 三唑环的方法。尽管细胞毒性一般且与亲脂性无关，但我们发现一种结构相似的浓缩核苷转运体2（CNT2）抑制剂具有适度的细胞毒性（MCF - 7细胞的半数抑制浓度为42μM）。这些合成方法可用于有效研究核碱基的变化。
