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

摘要

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.