Oxidized analogs of Di(1H-indol-3-yl)methyl-4-substituted benzenes are NR4A1-dependent UPR inducers with potent and safe anti-cancer activity.

ABSTRACT: Di(1H-indol-3-yl)(4-trifluoromethylphenyl)methane (DIM-Ph-4-CF₃) is an analog of orphan nuclear receptor 4A1 (NR4A1) ligand cytosporone B. We have synthesized several oxidation products of DIM-Ph-4-CF₃, focusing on analogs with electron-withdrawing or donating groups at their phenyl ring 4-positions, and examined their anti-cancer activity and mechanism-of-action. Mesylates (DIM-Ph-4-X⁺ OMs^-s) having CF₃, CO₂Me and Cl groups were more effective inhibitors of cancer cell viability than their precursors. ¹⁹F NMR spectroscopy and differential scanning calorimetry strongly indicated interactions of DIM-Ph-4-CF₃⁺ OMs^- with the NR4A1 ligand binding domain, and compound-induced apo

SUBMITTER: Sanchez M 

PROVIDER: S-EPMC5982742 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature