Synthesis and Bioactivity Evaluation of a Novel 1,2,4-Oxadiazole Derivative in vitro and in 3×Tg Mice

Alzheimer's disease (AD) is the most common neurodegenerative disease whose patients suffered from cognitive impairments. In our study, a novel 1,2,4-Oxadiazole derivative wyc-7-20 was synthesized, which showed low cytotoxicity and potent neuroprotective effect at the cellular level. Improved cognitive impairments, β-amyloid (Aβ) clearance, and tau pathological phenotypes were detected in transgenic animal models after wyc-7-20 treatment. Reversed expressions in AD-related genes were also detected. The

wyc-7-20 was potent in AD therapy.

Human neuroblastoma (SH-SY5Y) cells and human hepatocellular carcinoma (HepG2) cells were used to detect median lethal dose (LD50). H2O2 and Aβ1-42 oligomers (AβOs) were respectively, added into SH-SY5Y cells to detect anti-ROS (reactive oxygen species) and anti-AβOs effects of wyc-7-20. 3×Tg mice were administered with wyc-7-20, and then Y maze test and Morris water maze (MWM) test were applied to detect cognitive improvements. Brain tissue samples were subsequently collected and analyzed using different techniques.

The pathological complexity of AD increased difficulties in medical research. To explore a new potential medical treatment for AD, a novel 1,2,4-Oxadiazole derivative (wyc-7-20) was designed, synthesized to explore the application in this study. Materials and

wyc-7-20 showed low cytotoxicity and potent neuroprotective effect at the cellular level. Improved cognitive impairments, Aβ clearance, and tau pathological phenotypes were detected in transgenic animal models after wyc-7-20 treatment. Reversed expressions in AD-related genes were also detected.