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Mao Inhibitory Activity: 3-Phenylcoumarins versus 4-Hydroxy-3-Phenylcoumarins
Published: 12 November 2013 by MDPI in The 17th International Electronic Conference on Synthetic Organic Chemistry session Bioorganic, Medicinal and Natural Products
Abstract: Coumarins constitute an important class of benzopyrones of different origin. Due to their structural variability they occupy an important place in the realm of natural products and synthetic organic chemistry. Coumarins exhibit a broad range of biological activities such as anticoagulants, antimicrobials, antibacterials, anticancers, and anti-HIV. Furthermore several studies have paid special attention to their antioxidative and enzyme inhibitory properties.In particular some natural coumarins have shown a low monoamine oxidase (MAO) inhibitory potency while properly modified natural coumarins have been characterized as potent and selective MAO inhibitors. MAO is a FAD-depending enzyme found in the outer mitochondrial membrane of neuronal, glial and other mammalian cells. This enzyme is responsible for catalysing the oxidative deamination of dietary amines and neurotransmitters, regulating intracellular levels of biogenic amines in the brain and the peripheral tissues.Our research group has also reported high MAO-B selectivity with 6- or 8- substituted-3-arylcoumarin scaffolds. A variety of functional groups of diverse size, lipophilic and electronic properties were introduced in both aromatic rings, concluding that a small substitution at C6 or C8 of the coumarin nucleus is important if a phenyl group is located at C3. Substituents on the 3-phenyl ring also play a crucial role in activity and selectivity: meta and para substitutions are the most favorable for desired activity.Based on the previous 3-phenylcoumarins experimental results and with the aim of finding novel and selective MAO inhibitors in this paper we describe a new project with a comparative study between 3-phenylcoumarins and 3-phenyl-4-hydroxycoumarins.We have used the Perkin and Suzuki reaction as a key step of a good methodology for the efficient and general synthesis of a selected series of 3-phenylcoumarins and 4-hydroxy-3-phenylcoumarins. Most of the tested compounds exhibit a high affinity and selectivity for the MAO-B isoenzyme with values of IC50 better than reference compounds.
Keywords: MAO, 3-phenylcoumarins