Memoquin: a multi-target-directed ligand as an innovative therapeutic opportunity for Alzheimer's disease.
Alzheimer's disease is currently thought to be a complex, multifactorial syndrome, unlikely to arise from a single causal factor; instead, a number of related biological alterations are thought to contribute to its pathogenesis. This may explain why the currently available drugs, developed according to the classic drug discovery paradigm of "one-molecule-one-target," have turned out to be palliative. In light of this, drug combinations that can act at different levels of the neurotoxic cascade offer new avenues toward curing Alzheimer's and other neurodegenerative diseases. In parallel, a new strategy is emerging-that of developing a single chemical entity able to modulate multiple targets simultaneously. This has led to a new paradigm in medicinal chemistry, the "multi-target-directed ligand" design strategy, which has already been successfully exploited at both academic and industrial levels. As a case study, we report here on memoquin, a new molecule developed following this strategy. The in vitro and in vivo biological profile of memoquin demonstrates the suitability of the new strategy for obtaining innovative drug candidates for the treatment of neurodegenerative diseases.
Bolognesi
Maria Laura
ML
Department of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy.
Cavalli
Andrea
A
Melchiorre
Carlo
C
D000473:Alkanes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000577:Amides / Q000627:therapeutic use; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000840:Anisoles / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D001288:Attention / Q000187:drug effects; D002794:Choline / Q000378:metabolism; D015195:Drug Design; D005021:Ethylamines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005702:Galantamine / Q000627:therapeutic use; D006801:Humans; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D058225:Plaque, Amyloid / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D016875:tau Proteins / Q000378:metabolism
D000473:Alkanes; D000577:Amides; D016229:Amyloid beta-Peptides; D000840:Anisoles; D000975:Antioxidants; D005021:Ethylamines; D010975:Platelet Aggregation Inhibitors; C472793:caproctamine; C521476:memoquin; D016875:tau Proteins; D005702:Galantamine; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D002794:Choline