In silico identification of novel and selective monoamine oxidase B inhibitors
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Date
2013
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
SPRINGER WIEN
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.
Description
Keywords
Monoamine oxidase (MAO-A MAO-B), Inhibition, In silico screening, Molecular modelling, Docking, De novo design, Selective inhibitors
Turkish CoHE Thesis Center URL
Citation
7
WoS Q
Q2
Scopus Q
Q2
Source
Volume
120
Issue
6
Start Page
853
End Page
858