title: In silico identification of novel and selective monoamine oxidase B inhibitors.
abstract: Monoamine oxidases (MAO) A and B are flavin adenine dinucleotides containing enzymes bound to the mitochondrial outer membranes of the cells of the brain, liver, intestine, and placenta, as well as platelets. Recently, selective MAO-B inhibitors have received increasing attention due to their neuroprotective properties and the multiple roles they can play in the therapy of neurodegenerative disorders. This study was based on 10 scaffolds that were selected from more than a million lead compounds in the ZINCv12 lead library for their structural and physicochemical properties which inhibit MAO-B. Utilizing ZINC and Accelrys 3.1 fragment-based libraries, which contain about 400 thousand fragments, we generated 200 potential candidates. GOLD, LibDock, and AutoDock 4.02 were used to identify the inhibition constants and their position in the active sites of both MAO isozymes. The dispositions of the candidate molecules within the organism were checked with ADMET PSA 2D (polar surface area) against ADMET AlogP98 (the logarithm of the partition coefficient between n-octanol and water). The MAO-B inhibition activities of the candidates were compared with the properties of rasagiline which is known to be a selective inhibitor of MAO-B.
authors.affiliation: Department of Bioinformatics and Genetics, Faculty of Engineering and Natural Sciences, Kadir Has University, 34083 Fatih, Istanbul, Turkey. kyelekci@gmail.com
authors.forename: Kemal
authors.initials: K
authors.lastname: Yelekçi
authors.forename: Bora
authors.initials: B
authors.lastname: Büyüktürk
authors.forename: Nurdan
authors.initials: N
authors.lastname: Kayrak
mesh_terms: D000818:Animals; D003198:Computer Simulation; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000737:chemistry*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase