Browsing by Author "Karaman, Dilara"

Now showing 1 - 1 of 1

In Silico Design and Modeling of Coumarin Derivatives as Selective Monoamine Oxidase a Inhibitors
(Kadir Has Üniversitesi, 2014) Karaman, Dilara; Yelekçi, Kemal
Selective and reversible inhibition of Monoamine Oxidase (MAO) isoenzymes has an important place in treatment of various neurological disorders. Out of the two isoforms of Monoamine Oxidase enzymes inhibition of MAO-A have been giving positive results in treatment of depression and inhibition of MAO-B in cure of Parkinson’s disease. The difference in treatment is due to the fact that these two enzymes have different substrate specificities. in this study 125 different coumarin derivatives were designed by adding 5 different side groups to 3rd 5th 7th positions of coumarin nucleus. These coumarin derivatives were tested in terms of affinity to MAO enzymes by using computational methods in silico. Using to AutoDock4.2 docking software’s results we have found that most of these derivatives had affinity for both MAO-A and MAO-B enzymes at nanomolar and micromolar levels. At the same time we have seen that the coumarin derivatives had more inhibition properties with MAO-A. Binding properties of each the best five derivatives for MAO-A and MAO-B were examined comprehensively by using Accelrys Discovery Studio software. According to these results M123 ligand might be the best coumarin derivative in the 125 ligands because M123 ligand was the best second inhibitor and the most selective inhibitor. Other results from this study showed that while using phenyl as side group increased the selectivity using of phenyl and bromine increased the affinity to MAO-B but also decreased the selectivity. This study demonstrates that coumarin derivatives having particular phenyl at 7th position are effective at the MAO-A inhibition and coumarin derivatives that will be improved in this direction may be candidates in treatment of depression. -- Abstract'tan.