title: Design, synthesis and biological evaluation of benzyloxyphenyl-methylaminophenol derivatives as STAT3 signaling pathway inhibitors.
abstract: STAT3 signaling pathway has been validated as a vital therapeutic target for cancer therapy. Based on the novel STAT3 inhibitor of a benzyloxyphenyl-methylaminophenol scaffold hit (1) discovered through virtual screening, a series of analogues had been designed and synthesized for more potent inhibitors. The preliminary SAR had been discussed and the unique binding site in SH2 domain was predicted by molecular docking. Among them, compounds 4a and 4b exhibited superior activities than hit compound (1) against IL-6/STAT3 signaling pathway with IC50values as low as 7.71μM and 1.38μM, respectively. Compound 4a also displayed potent antiproliferative activity against MDA-MB-468 cell line with an IC50value of 9.61μM. We believe that these benzyloxyphenyl-methylaminophenol derivatives represent a unique mechanism for interrogating STAT3 as well as a potential structure type for further exploration.
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Dingding
authors.initials: D
authors.lastname: Gao
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: zmmworld@gmail.com.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: liyx417@fudan.edu.cn.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Li
keywords: Benzyloxyphenyl-methylaminophenol derivatives; Inhibitors; STAT3 signaling pathway; Structure–activity relationship