title: Imine resveratrol analogues: molecular design, Nrf2 activation and SAR analysis.
abstract: Resveratrol is a natural phenol with protective effects against cancer and inflammation-related diseases. Its mechanism of action involves the activation of nuclear factor E2 p45-related factor 2 (Nrf2), which plays a key role in regulation of genes driven by antioxidant response element (ARE). Inspired by the effect of resveratrol, here we synthesized a series of imine resveratrol analogs (IRAs), evaluated their abilities to activate Nrf2 by using cell based ARE-reporter assay. After the first-round screening, preliminary and quantitative structure-activity relationship (SAR) was analyzed, and the structural features determining Nrf2 activation ability were proposed. Two novel IRAs were designed and subsequently synthesized, namely 2-methoxyl-3,6-dihydroxyl-IRA and 2,3,6-trihydroxyl-IRA. They were proved to be the most potent Nrf2 activators among the IRAs.
authors.affiliation: Department of Chemistry, Zhejiang University, Hangzhou, P. R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Chemistry, Zhejiang University, Hangzhou, P. R. China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, P. R. China.
authors.forename: Xiu Jun
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Zhejiang University, Hangzhou, P. R. China.
authors.forename: Yuanjiang
authors.initials: Y
authors.lastname: Pan
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D007097:Imines / Q000737:chemistry*; D061986:MCF-7 Cells; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D020218:Response Elements / Q000187:drug effects; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D007097:Imines; D051267:NF-E2-Related Factor 2; D013267:Stilbenes; D000077185:Resveratrol