Identification and Structure-Activity Studies of 1,3-Dibenzyl-2-aryl imidazolidines as Novel Hsp90 Inhibitors.

ABSTRACT: Hsp90 (Heat shock protein 90) is involved in various processes in cancer occurrence and development, and therefore represents a promising drug target for cancer therapy. In this work, a virtual screening strategy was employed, leading to the identification of a series of compounds bearing a scaffold of 1,3-dibenzyl-2-aryl imidazolidine as novel Hsp90 inhibitors. Compound 4a showed the highest binding affinity to Hsp90α (IC₅₀ = 12 nM) in fluorescence polarization (FP) competition assay and the strongest anti-proliferative activity against human breast adenocarcinoma cell line (MCF-7) and human lung epithelial cell line (A549) with IC₅₀ values of 21.58 μM and 31.22 μM, respectively. Western blotting assays revealed that these novel Hsp90 inhibitors significantly

SUBMITTER: Liu Y 

PROVIDER: S-EPMC6600241 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature