title: Targeting monoamine oxidases with multipotent ligands: an emerging strategy in the search of new drugs against neurodegenerative diseases.
abstract: The socioeconomic burden of multi-factorial pathologies, such as neurodegenerative diseases (NDs), is enormous worldwide. Unfortunately, no proven disease-modifying therapy is available yet and in most cases (e.g., Alzheimer's and Parkinson's disease) the approved drugs exert only palliative and symptomatic effects. Nowadays, an emerging strategy for the discovery of disease-modifying drugs is based on the multi-target directed ligand (MTDL) design, an innovative shift from the traditional approach one-drug-one-target to the more ambitious one-drug-more-targets goal. Herein, we review the discovery strategy, the mechanism of action and the biopharmacological evaluation of multipotent ligands exhibiting monoamine oxidase (MAO) inhibition as the core activity with a potential for the treatment of NDs. In particular, MAO inhibitors exhibiting additional acetylcholinesterase (AChE) or nitric oxide synthase (NOS) inhibition, or ion chelation/antioxidant-radical scavenging/anti-inflammatory/A2A receptor antagonist/APP processing modulating activities have been thoroughly examined.
authors.affiliation: Dipartimento Farmacochimico, Universita degli Studi di Bari "Aldo Moro", Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pisani
authors.forename: M
authors.initials: M
authors.lastname: Catto
authors.forename: F
authors.initials: F
authors.lastname: Leonetti
authors.forename: O
authors.initials: O
authors.lastname: Nicolotti
authors.forename: A
authors.initials: A
authors.lastname: Stefanachi
authors.forename: F
authors.initials: F
authors.lastname: Campagna
authors.forename: A
authors.initials: A
authors.lastname: Carotti
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000737:chemistry / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000188:drug therapy; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry / Q000627:therapeutic use; D002614:Chelating Agents / Q000737:chemistry / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D016166:Free Radical Scavengers / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007189:Indans; D008024:Ligands; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D016564:Amyloid beta-Protein Precursor; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002614:Chelating Agents; D002800:Cholinesterase Inhibitors; D016166:Free Radical Scavengers; D007189:Indans; D008024:Ligands; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline; D019001:Nitric Oxide Synthase