Coumarin: A Natural, Privileged and Versatile Scaffold for Bioactive Compounds

• Published in: Molecules (Basel, Switzerland) Vol. 23; no. 2; p. 250
• Main Authors: Stefanachi, Angela, Leonetti, Francesco, Pisani, Leonardo, Catto, Marco, Carotti, Angelo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27-01-2018; MDPI
• Subjects: Alzheimer Disease - drug therapy; Alzheimer's disease; Amine oxidase (flavin-containing); Aromatase; Aromatase - chemistry; Aromatase - metabolism; Bioactive compounds; Biosynthesis; Biotransformation; Breast cancer; Chemists; Cholinesterase; Cholinesterases - chemistry; Cholinesterases - metabolism; Coumarin; Coumarins - chemical synthesis; Coumarins - pharmacology; Drug Design; Enzyme inhibitors; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Estrogens; Humans; Molecular Structure; Monoamine Oxidase - chemistry; Monoamine Oxidase - metabolism; Neuroprotective Agents - chemical synthesis; Neuroprotective Agents - pharmacology; Nootropic Agents - chemical synthesis; Nootropic Agents - pharmacology; Parkinson Disease - drug therapy; Parkinson's disease; Pharmacology; Review; Reviews; Scaffolds; Structure-Activity Relationship; aromatase inhibitors; cholinesterase inhibitors; monoamine oxidase inhibitors; multitarget ligands; coumarin
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23020250

Many naturally occurring substances, traditionally used in popular medicines around the world, contain the coumarin moiety. Coumarin represents a privileged scaffold for medicinal chemists, because of its peculiar physicochemical features, and the versatile and easy synthetic transformation into a large variety of functionalized coumarins. As a consequence, a huge number of coumarin derivatives have been designed, synthesized, and tested to address many pharmacological targets in a selective way, e.g., selective enzyme inhibitors, and more recently, a number of selected targets (multitarget ligands) involved in multifactorial diseases, such as Alzheimer's and Parkinson's diseases. In this review an overview of the most recent synthetic pathways leading to mono- and polyfunctionalized coumarins will be presented, along with the main biological pathways of their biosynthesis and metabolic transformations. The many existing and recent reviews in the field prompted us to make some drastic selections, and therefore, the review is focused on monoamine oxidase, cholinesterase, and aromatase inhibitors, and on multitarget coumarins acting on selected targets of neurodegenerative diseases.