The translocator protein ligands as mitochondrial functional modulators for the potential anti-Alzheimer agents

Small molecule modulators of mitochondrial function have been attracted much attention in recent years due to their potential therapeutic applications for neurodegenerative diseases. The translocator protein (TSPO) is a promising target such compounds, given its involvement the formation permeability transition pore response stress. In this study, we performed ligand-based pharmacophore design and virtual screening, identified potent hit compound, 7 (VH34) as TSPO ligand. After validating biological activity against amyloid-β (Aβ) induced dysfunction acute transgenic Alzheimer’s disease (AD) model mice, developed library analogs, found two most active 31 44, which restored membrane potential, ATP production, cell viability under Aβ-induced toxicity. These compounds recovered learning memory AD mice with improved pharmacokinetic properties.