Quantum chemical analysis of potential anti-Parkinson agents

Journal of Chemical Sciences

Ahmad Ebadi¹  Azam Bagheri¹  Nima Razzaghi-Asl1 2²  Sara Shahabipour² 

[1] Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran$$;Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran, PO code: 5618953141$$

关键词: MAO-B;    Coumarin;    Molecular docking;    Quantum mechanical calculation.;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

Monoamine oxidases (MAOs) are amine oxidoreductase falvoenzymes that belong to the integral proteins of the outer mitochondrial membrane. MAO exists in two distinct isoforms; MAO-A and MAO-B. Inhibition of MAO-A and MAO-B is important for developing antidepressant and antiparkinson agents, respectively. In the light of the above explanations, detailed structure binding relationship studies on the intermolecular binding components of MAO-B complexes may unravel the way toward developing novel anti-Parkinson agents. In the present contribution, intermolecular binding pattern for a series of experimentally validated 3-arylcoumarin MAO-B inhibitors (1–9) have been elucidated via molecular docking and density functional theory (DFT) calculations. Intermolecular binding energy components could not be analyzed by docking and due to this limitation, quantum mechanical (QM) calculations including functional B3LYP in association with split valence basis set (Def2-SVP) were applied to estimate the ligand-residue binding energies in the MAO-B active site. Moreover; results were interpreted in terms of calculated polarization effects that were induced by individual amino acids of the MAO-B active site. The results of the present study provide an approach to pharmacophore-based modification within the 3-arylcoumarin scaffold for potent MAO-B inhibitors.

【 授权许可】

Unknown