Ethenesulfonyl fluoride derivatives as telomerase inhibitors: structure-based design, SAR, and anticancer evaluation in vitro. (1st January 2018)

• Record Type: Journal Article
• Authors: Chen, Xing; Zha, Gao-Feng; Wang, Jie Quan; Liu, Xin-Hua
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 33:Number 1(2018)
• Page Start: 1266
• Page End: 1270
• Publication Date: 2018-01-01
• Subjects: Ethenesulfonyl fluoride -- selective anticancer activity -- telomerase -- inhibitor; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2018.1484735
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Based on our previous docking model, in order to carry out more rational drug design, totally 82 vinyl sulfonyl fluorides, including some 2-(hetero)arylethenesulfonyl fluorides and 1, 3-dienylsulfonyl fluorides derivatives as potential human telomerase inhibitors were designed and synthesised. The in vitro anticancer activity assay showed that compound57 (1 E, 3 E )-4-(4-(( E )-2-(fluorosulfonyl)vinyl)phenyl)buta-1, 3-diene-1-sulfonyl fluoride exhibited high activity against A375 and MDA-MB-231 cell lines with IC50 1.58 and 3.22 µM, but it manifested obvious un-toxic effect against GES-1 and L-02 with IC50 with IC50 values less than 2.00 mM. By the modified TRAP assay, some compounds including57 exhibited potent inhibitory activities against telomerase with IC50 values of 0.71–0.97 µM.