Design, Synthesis, and Evaluation of Orally Available Clioquinol-Moracin M Hybrids as Multitarget-Directed Ligands for Cognitive Improvement in a Rat Model of Neurodegeneration in Alzheimer’s Disease

• Published in: Journal of medicinal chemistry Vol. 58; no. 21; pp. 8616 - 8637
• Main Authors: Wang, Zhiren, Wang, Yali, Wang, Bo, Li, Wenrui, Huang, Ling, Li, Xingshu
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 12.11.2015; Amer Chemical Soc
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Amyloid beta-Peptides - antagonists & inhibitors; Amyloid beta-Peptides - metabolism; Animals; Antioxidants - chemistry; Antioxidants - therapeutic use; Benzofurans - chemistry; Benzofurans - therapeutic use; Chemistry, Medicinal; Clioquinol - analogs & derivatives; Clioquinol - therapeutic use; Cognition - drug effects; Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - physiopathology; Life Sciences & Biomedicine; Ligands; Male; Memory - drug effects; Models, Molecular; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotective Agents - chemistry; Neuroprotective Agents - therapeutic use; Pharmacology & Pharmacy; Phosphodiesterase 4 Inhibitors - chemistry; Phosphodiesterase 4 Inhibitors - therapeutic use; Protein Aggregates - drug effects; Rats; Rats, Wistar; Resorcinols - chemistry; Resorcinols - therapeutic use; Science & Technology; TARGET; AMYLOID-BETA PEPTIDE; PHOSPHODIESTERASE-4 INHIBITORS; SMALL MOLECULES; ACETYLCHOLINESTERASE; ANTIOXIDANT; BIOLOGICAL EVALUATION; HIGHLY POTENT; DERIVATIVES; AGGREGATION

A novel series of clioquinol-moracin hybrids were designed and synthesized by fusing the pharmacophores of clioquinol and moracin M, and their activities as multitarget-directed ligands against Alzheimer’s disease were evaluated. Biological activity results demonstrated that these hybrids possessed...