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

Abstract

Aim 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 results demonstrated wyc-7-20 was potent in AD therapy. Purpose 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 Methods Human neuroblastoma (SH-SY5Y) cells and human hepatocellular carcinoma (HepG2) cells were used to detect median lethal dose (LD50). H 2 O 2 and Aβ 1–42 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. Results 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. Conclusion wyc-7-20 was potent in AD therapy.

A neuron‐specific Isca1 knockout rat developments multiple mitochondrial dysfunction syndromes

“…Entry to an arm was confirmed when the four limbs of the rat were within the arm. 18 The sequence that the rat entered different arms was recorded by VisuTrack software, which recognized a spontaneous alternation, such as A‐B‐C or C‐A‐B. Alterative rate (%) = alternative number/(total entry −2) × 100%.…”

“…The rat was released at the end of one arm and allowed to explore freely in the three arms for 5 min. Entry to an arm was confirmed when the four limbs of the rat were within the arm 18 . The sequence that the rat entered different arms was recorded by VisuTrack software, which recognized a spontaneous alternation, such as A‐B‐C or C‐A‐B.…”