Ethenesulfonyl fluoride derivatives as telomerase inhibitors: structure-based design, SAR, and anticancer evaluation in vitro

• Main Authors: Xing Chen, Gao-Feng Zha, Jie Quan Wang, Xin-Hua Liu
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2018-01-01
• Series: Journal of Enzyme Inhibition and Medicinal Chemistry
• Subjects: Ethenesulfonyl fluoride; selective anticancer activity; telomerase; inhibitor
• Online Access: http://dx.doi.org/10.1080/14756366.2018.1484735
• ISSN: 1475-6366; 1475-6374

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 compound 57 (1E,3E)-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 including 57 exhibited potent inhibitory activities against telomerase with IC50 values of 0.71–0.97 µM.