Nrf2/HO-1 activator 2 (compound 13m), a difluoro-substituted derivative, is a highly potent activator of Nrf2/HO-1. It exhibits substantial neuroprotective and antioxidant properties by activating the Nrf2/HO-1 pathway through phosphorylation of ERK1/2, JNK, or Akt in PC12 cells. This compound finds utility in the investigation of Parkinson's disease (PD) [1].

Nrf2/HO-1 activator 2 (compound 13m; 0.1-30 μM; 24 h) has protection to PC12 cells against toxicity and inhibits 6-OHDA- and Rotenone - induced cell death [1]. Nrf2/HO-1 activator 2 (1-100 μM; 11 h) inhibits 6-OHDA- or rotenone-induced production of reactive oxygen species and partially attenuates lipid peroxidation in rat brain homogenates. Nrf2/HO-1 activator 2 inhibits the production of lipid peroxide in rat brain homogenates by 28.8% at 100 μM [1]. Nrf2/HO-1 activator 2 (1-100 μM; 11 h) up-regulates heme oxygenase-1 (HO-1) and Nrf2 expression [1]. Nrf2/HO-1 activator 2 (10 μM; 2-3 h; PC12 cells) activator 2 activates Nrf2/HO-1 signaling by phosphorylated ERK1/2, JNK, and Akt [1]. Cell Viability Assay [1] Cell Line: PC12 cells Concentration: 3, 5, 7, 10 and 30 μM, 6-OHDA (50 μM); 0.1, 0.3, 1, 3, 10, and 30 μM, Rotenone (1 μM) Incubation Time: 24 hours Result: Exhibited neuroprotective effects on 6-OHDA-induced toxicity in dose-dependent manners. Rescued cells from rotenone-induced damage, with increased levels of cell viability up to 79.9% at 30 μM. Western Blot Analysis [1] Cell Line: PC12 cells Concentration: 0, 1, 3, 10, and 30 μM Incubation Time: 24 hours Result: Upregulated HO-1 levels in a dose-dependent manner, with 1.5- and 2-fold increases at 30 μM concentrations, respectively. Enhanced the nuclear translocation of Nrf2 in PC12 cells after 3 h at 10 μM. Western Blot Analysis [1] Cell Line: PC12 cells Concentration: 10 μM Incubation Time: 2-3 hours Result: Induced the phosphorylation of ERK1/2, JNK, and Akt.