Irreversible Inhibition of Monoamine Oxidase B by the Antiparkinsonian Medicines Rasagiline and Selegiline: A Computational Study (Eur. J. Org. Chem. 32/2011)

The cover picture shows the importance of understanding the mechanism of monoamine oxidase B inhibition for the development of novel and improved antiparkinsonian drugs. Computational analysis of seven inhibition mechanisms elucidated the most plausible one. It involves the nucleophilic attack of the deprotonated inhibitor onto the enzyme's cofactor FAD, following enzymatic proton detachment from the inhibitor's terminal acetylene carbon. This reaction forms a therapeutical basis for relieving the symptoms of Parkinson disease. Mechanism-based inhibitors of enzymes, being highly specific, often prove to be promising drug candidates. Details are discussed in the article by R. Vianello et al. on p. 6419 ff.