Kim, TaeHun Morshed, Mohammad N. Londhe, Ashwini M. Lim, Ji W. Lee, Ha E. Cho, Suengmok Cho, Sung J. Hwang, Hayoung Lim, Sang M. Lee, Jae Y. Lee, Jiyoun Pae, Ae N. 2024-01-19T15:33:48Z 2024-01-19T15:33:48Z 2022-01-25 2021-01 1475-6366 https://pubs.kist.re.kr/handle/201004/117567 Small molecule modulators of mitochondrial function have been attracted much attention in recent years due to their potential therapeutic applications for neurodegenerative diseases. The mitochondrial translocator protein (TSPO) is a promising target for such compounds, given its involvement in the formation of the mitochondrial permeability transition pore in response to mitochondrial stress. In this study, we performed a ligand-based pharmacophore design and virtual screening, and identified a potent hit compound, 7 (VH34) as a TSPO ligand. After validating its biological activity against amyloid-beta (A beta) induced mitochondrial dysfunction and in acute and transgenic Alzheimer's disease (AD) model mice, we developed a library of analogs, and we found two most active compounds, 31 and 44, which restored the mitochondrial membrane potential, ATP production, and cell viability under A beta-induced mitochondrial toxicity. These compounds recovered learning and memory function in acute AD model mice with improved pharmacokinetic properties. English TAYLOR & FRANCIS LTD The translocator protein ligands as mitochondrial functional modulators for the potential anti-Alzheimer agents Article 10.1080/14756366.2021.1900158 1 JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, v.36, no.1, pp.831 - 846 JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY 36 1 831 846 N scie scopus 000631656700001 2-s2.0-85103041222 Biochemistry & Molecular Biology Chemistry, Medicinal Biochemistry & Molecular Biology Pharmacology & Pharmacy Article Alzheimer&#8217 s disease &#160 function modulators translocator protein ligand