Synthesis and Biological Evaluation of DIDS Analogues as Efficient Inhibitors of RAD51 Involved in Homologous Recombination
作者:Alexandre Demeyer、Lucie Fonteneau、Marion Liennard、Claire Foyer、Pierre Weigel、Adèle Laurent、Jacques Lebreton、Fabrice Fleury、Monique Mathé-Allainmat
DOI:10.1016/j.bmcl.2023.129261
日期:2023.3
2′-disulfonic acid (DIDS), two series of analogues with small or bulky substituents on the aromatic parts of the stilbene moiety were prepared for a structure–activity relationship study. Three compounds, the cyano analogue (12), and benzamide (23) or phenylcarbamate (29) analogues of DIDS were characterized as novel potent RAD51 inhibitors with HR inhibition in the micromolar range.
RAD51 是同源重组 DNA 修复途径的关键蛋白,在某些癌细胞中过表达,从而破坏了癌症治疗的效率。RAD51 抑制剂的开发似乎是一种有前途的解决方案,可以恢复这些癌细胞对放疗或化疗的敏感性。从被鉴定为 RAD51 调节剂的小分子 4,4'-二异硫氰基芪-2,2'-二磺酸 (DIDS),制备了在茋部分的芳香部分上具有小或大取代基的两个系列类似物,用于构效关系研究。三种化合物,氰基类似物 ( 12 ) 和苯甲酰胺 ( 23 ) 或氨基甲酸苯酯 ( 29) DIDS 的类似物被表征为新型强效 RAD51 抑制剂,在微摩尔范围内具有 HR 抑制作用。