Discovery of potent and reversible MAO-B inhibitors as furanochalcones
| Autor: | Bijo Mathew, Jerad Suresh, Hoon Kim, Seung Cheol Baek, Surya Parakkot Ramakrishnan |
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| Rok vydání: | 2018 |
| Předmět: |
Chalcone
Monoamine Oxidase Inhibitors Stereochemistry Monoamine oxidase Molecular Conformation Molecular Dynamics Simulation 01 natural sciences Biochemistry Structure-Activity Relationship chemistry.chemical_compound Chalcones Non-competitive inhibition Structural Biology Drug Discovery Humans Binding site Monoamine Oxidase Molecular Biology Binding Sites 010405 organic chemistry General Medicine 0104 chemical sciences Molecular Docking Simulation Kinetics 010404 medicinal & biomolecular chemistry chemistry Lazabemide Monoamine oxidase B Selectivity Lead compound Protein Binding |
| Zdroj: | International Journal of Biological Macromolecules. 108:660-664 |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2017.11.159 |
| Popis: | A series of twelve furanochalcones (F1-F12) was synthesized and investigated for their human monoamine oxidase inhibitory activities. Among the series, compound (2E, 4E)-1-(furan-2-yl)-5-phenylpenta-2, 4-dien-1-one (F1), which was analyzed by single-crystal X-ray diffraction, showed potent and selective MAO-B inhibitory activity with an inhibition constant (Ki) value of 0.0041 μM and selectivity index of (SI) 172.4, and exhibited competitive inhibition. Introduction of a cinnamyl group to the furanochalcone significantly increased the inhibitory activity. In the dilution-recovery experiments, the residual activities of MAO-A and MAO-B by F1 under the diluted condition fully recovered as compared with the undiluted condition, indicating F1 is a reversible inhibitor. The Ki value of F1 is the lowest among the values of chalcone derivatives and furthermore lower than that (0.0079 μM) of the reversible MAO-B inhibitor, lazabemide, a marketed drug. Molecular docking study against hMAO-B provided the binding site interactions of the lead compound, including strong π-π stacking between the phenyl system and FAD nucleus. |
| Databáze: | OpenAIRE |
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