Discovery of Potent Cholinesterase Inhibition-Based Multi-Target-Directed Lead Compounds for Synaptoprotection in Alzheimer’s Disease

• Published in: Journal of medicinal chemistry Vol. 65; no. 18; pp. 12292 - 12318
• Main Authors: Turgutalp, Bengisu, Bhattarai, Prabesh, Ercetin, Tugba, Luise, Chiara, Reis, Rengin, Gurdal, Enise Ece, Isaak, Andreas, Biriken, Derya, Dinter, Elisabeth, Sipahi, Hande, Schepmann, Dirk, Junker, Anna, Wünsch, Bernhard, Sippl, Wolfgang, Gulcan, Hayrettin Ozan, Kizil, Caghan, Yarim, Mine
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 22.09.2022; Amer Chemical Soc
• Subjects: Acetylcholinesterase - metabolism; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Animals; Chemistry, Medicinal; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Cholinesterase Inhibitors - therapeutic use; Cholinesterases; Donepezil - therapeutic use; Lead - therapeutic use; Life Sciences & Biomedicine; Ligands; Pharmacology & Pharmacy; Science & Technology; Zebrafish - metabolism; P2X7 RECEPTOR; TARGET; EXCITOTOXICITY; NMDA RECEPTORS; MOUSE MODEL; SIGMA-1 RECEPTOR; D-ASPARTATE RECEPTOR; SYNAPTIC PLASTICITY; BINDING; LIFE EXPECTANCY

Drug development efforts that focused on single targets failed to provide effective treatment for Alzheimer’s disease (AD). Therefore, we designed cholinesterase inhibition (ChEI)-based multi-target-directed ligands (MTDLs) to simultaneously target AD-related receptors. We built a library of 70 comp...