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Abstract
It is well known that monoamine oxidase (MAO) plays a pivotal role in neurodegeneration and the inhibition of this enzyme can manifest anti-depressant properties as well as have a positive impact in Alzheimer’s and Parkinson’s diseases. Specifically, the MAO enzyme catalyzes the oxidative deamination of a variety of monoamines. This reaction leads to the formation of aldehydes, together with H2O2 and ammonia. Hydrogen peroxide can generate additional reactive oxygen species (ROS), this way leading to neurotoxicity. When MAO is activated, it induces the amyloid-beta (Aβ) deposition via abnormal cleavage of the amyloid precursor protein (APP) and contributes to the generation of neurofibrillary tangles and cognitive impairment due to neuronal loss. MAO has two isoforms: MAO-A and MAO-B. The main hMAO-B inhibitors used for the treatment of Alzheimer’s and Parkinson’s diseases, encompass a terminal triple bond in their structure, which provides their potency. Recently, a new class of inhibitors has emerged, bearing the carbon-carbon triple bond not necessarily at the end of the chain. In this review, the structure and physiological function of the MAO enzymes is discussed, as well as their mechanism of inhibition via terminal propargylamines. Moreover, it is highlighted the current development and discovery of potential hMAO-B inhibitors from propargylamine scaffolds and docking studies are performed to four of them by our group, in order to assess their binding energy with the enzyme. Finally, molecules which do not contain a propargylamine moiety in their structure were studied and compared against a known hMAO-B inhibitor, deprenyl. From the superimposition results of these molecules with deprenyl, as well as the interactions of the molecules with the amino acids of the active site of hMAO-B, it appears that these compounds have several similarities with deprenyl, opening new paths for the creation of novel molecules against Alzheimer’s disease.
