Open AccessMao Inhibitory Activity: 3-Phenylcoumarins versus 4-Hydroxy-3-Phenylcoumarins
Author(s) -
Giovanna Delogu,
Silvia Serra,
Dolores Viña
Publication year - 2013
Language(s) - English
Resource type - Conference proceedings
DOI - 10.3390/ecsoc-17-b023
Subject(s) - monoamine oxidase , chemistry , coumarin , stereochemistry , enzyme , monoamine oxidase b , oxidative deamination , structure–activity relationship , inhibitory postsynaptic potential , biochemistry , in vitro , biology , organic chemistry , neuroscience
Coumarins constitute an important class of benzopyrones of different origin. Due to their structural\udvariability they occupy an important place in the realm of natural products and synthetic organic chemistry. Coumarins\udexhibit a broad range of biological activities such as anticoagulants, antimicrobials, antibacterials, anticancers, and anti-\udHIV. Furthermore several studies have paid special attention to their antioxidative and enzyme inhibitory properties.\udIn particular some natural coumarins have shown a low monoamine oxidase (MAO) inhibitory potency while\udproperly modified natural coumarins have been characterized as potent and selective MAO inhibitors. MAO is a FAD-\uddepending enzyme found in the outer mitochondrial membrane of neuronal, glial and other mammalian cells. This\udenzyme is responsible for catalysing the oxidative deamination of dietary amines and neurotransmitters, regulating\udintracellular levels of biogenic amines in the brain and the peripheral tissues.\udOur research group has also reported high MAO-B selectivity with 6- or 8- substituted-3-arylcoumarin scaffolds. A\udvariety of functional groups of diverse size, lipophilic and electronic properties were introduced in both aromatic rings,\udconcluding that a small substitution at C6 or C8 of the coumarin nucleus is important if a phenyl group is located at C3.\udSubstituents on the 3-phenyl ring also play a crucial role in activity and selectivity: meta and para substitutions are the\udmost favorable for desired activity.\udBased on the previous 3-phenylcoumarins experimental results and with the aim of finding novel and selective MAO\udinhibitors in this paper we describe a new project with a comparative study between 3-phenylcoumarins and 3-phenyl-\ud4-hydroxycoumarins.\udWe have used the Perkin and Suzuki reaction as a key step of a good methodology for the efficient and general\udsynthesis of a selected series of 3-phenylcoumarins and 4-hydroxy-3-phenylcoumarins. Most of the tested compounds\udexhibit a high affinity and selectivity for the MAO-B isoenzyme with values of IC 50 better than reference compounds