Electrophilic fatty acid nitroalkenes regulate Nrf2 and NF-κB signaling:A medicinal chemistry investigation of structure-function relationships.

ABSTRACT: Fatty acid nitroalkene derivatives (NO2-FA) activate Nrf2-regulated antioxidant gene expression and inhibit NF-κB-dependent cytokine expression. To better define NO2-FA structure-function relationships, a series of 22 new chemical entities (NCEs) containing an electrophilic nitroalkene functional group were synthesized and screened for both Nrf2- and NF-κB activities using luciferase-based assays. The structural variables were acyl chain length (11 to 24 carbons) and position of the electrophilic nitroalkene group. In luciferase-based reporter assays, Nrf2 was maximally activated by omega-12 nitroalkene fatty acids while TNFα stimulated NF-κB-inhibition was maximal for omega-5 nitroalkenes. The top pathway-modulating NO2-FAs were a) evaluated for an ability to activate Nrf2-dependent signa

SUBMITTER: Khoo NKH 

PROVIDER: S-EPMC5797128 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature