A structural approach to investigate halogen substituted MAO-B inhibitors using QSAR modeling,molecular dynamics,and conceptual DFT analysis |
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| Affiliation: | 1. Department of Basic Medical Sciences, College of Applied Medical Sciences in Khamis Mushait, King Khalid University, Abha, Saudi Arabia;2. Department of Pharmaceutical Chemistry, Prof. Ravindra Nikam College of Pharmacy, Gondur, Dhule 424002, Maharashtra, India;3. Division of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India;4. Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, India;5. Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India;6. Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea |
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| Abstract: | 
Halogenated inhibitors showed robust, reversible, and selective monoamine oxidase-B (MAO-B) inhibitory efficacy in candidates that were derived from them. Our team has previously synthesized and assessed a panel of halogenated chalcones and coumarin for the study on MAO-B inhibition. The aim of this study was to build GA-MLR based QSAR models and predictive 3D Pharmacophore models, as well as to investigate the relationship between halogenated derivatives and MAO-B inhibitory activity. The robust statistical significance in the parameter (R2 = 0.78 and Q2 = 0.69) was demonstrated. Best Hypo1 contains one hydrophobic and two aromatic rings. The lead molecule for quantum mechanics was performed, and it was revealed that it would bind to proteins and provide stability. To determine the stability of the ligand-enzyme complex, a thorough molecular dynamics analysis of the lead compounds was accomplished. |
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| Keywords: | Monoamine oxidase-B Halogen QSAR Molecular dynamic Pharmacophore modelling Density functional theory MAO" },{" #name" :" keyword" ," $" :{" id" :" k0040" }," $$" :[{" #name" :" text" ," _" :" monoamine oxidase PD" },{" #name" :" keyword" ," $" :{" id" :" k0050" }," $$" :[{" #name" :" text" ," _" :" Parkinson’s disease AD" },{" #name" :" keyword" ," $" :{" id" :" k0060" }," $$" :[{" #name" :" text" ," _" :" Alzheimer’s disease hMAO" },{" #name" :" keyword" ," $" :{" id" :" k0070" }," $$" :[{" #name" :" text" ," _" :" human monoamine oxidase ROS" },{" #name" :" keyword" ," $" :{" id" :" k0080" }," $$" :[{" #name" :" text" ," _" :" reactive oxygen species AChE" },{" #name" :" keyword" ," $" :{" id" :" k0090" }," $$" :[{" #name" :" text" ," _" :" acetylcholinesterase SAR" },{" #name" :" keyword" ," $" :{" id" :" k0100" }," $$" :[{" #name" :" text" ," _" :" structure activity relationship BACE" },{" #name" :" keyword" ," $" :{" id" :" k0110" }," $$" :[{" #name" :" text" ," _" :" β-site amyloid precursor cleaving enzyme BChE/ BuChE" },{" #name" :" keyword" ," $" :{" id" :" k0120" }," $$" :[{" #name" :" text" ," _" :" butyrlcholinestrase FDA" },{" #name" :" keyword" ," $" :{" id" :" k0130" }," $$" :[{" #name" :" text" ," _" :" food and drug administration GA-MLR" },{" #name" :" keyword" ," $" :{" id" :" k0140" }," $$" :[{" #name" :" text" ," _" :" genetic algorithm-multiple linear regression method 3D-QSAR" },{" #name" :" keyword" ," $" :{" id" :" k0150" }," $$" :[{" #name" :" text" ," _" :" 3-dimensional quantitative structure-activity relationships correlation coefficient RMSD" },{" #name" :" keyword" ," $" :{" id" :" k0170" }," $$" :[{" #name" :" text" ," _" :" root mean square deviations HBA" },{" #name" :" keyword" ," $" :{" id" :" k0180" }," $$" :[{" #name" :" text" ," _" :" hydrogen bond acceptor HBD" },{" #name" :" keyword" ," $" :{" id" :" k0190" }," $$" :[{" #name" :" text" ," _" :" hydrogen bond donor MD" },{" #name" :" keyword" ," $" :{" id" :" k0200" }," $$" :[{" #name" :" text" ," _" :" molecular dynamics IBC" },{" #name" :" keyword" ," $" :{" id" :" k0210" }," $$" :[{" #name" :" text" ," _" :" inhibitor binding cavity DCCM" },{" #name" :" keyword" ," $" :{" id" :" k0220" }," $$" :[{" #name" :" text" ," _" :" dynamic cross correlation matrix PCA" },{" #name" :" keyword" ," $" :{" id" :" k0230" }," $$" :[{" #name" :" text" ," _" :" principal component analysis MM-GBSA" },{" #name" :" keyword" ," $" :{" id" :" k0240" }," $$" :[{" #name" :" text" ," _" :" molecular mechanics with generalised born and surface area solvation HOMO" },{" #name" :" keyword" ," $" :{" id" :" k0250" }," $$" :[{" #name" :" text" ," _" :" highest occupied molecular orbital LUMO" },{" #name" :" keyword" ," $" :{" id" :" k0260" }," $$" :[{" #name" :" text" ," _" :" lowest unoccupied molecular orbital MEPs" },{" #name" :" keyword" ," $" :{" id" :" k0270" }," $$" :[{" #name" :" text" ," _" :" molecular electrostatic potential surfaces FMOs" },{" #name" :" keyword" ," $" :{" id" :" k0280" }," $$" :[{" #name" :" text" ," _" :" frontier molecular orbitals FRT" },{" #name" :" keyword" ," $" :{" id" :" k0290" }," $$" :[{" #name" :" text" ," _" :" fisher’s randomization test RA" },{" #name" :" keyword" ," $" :{" id" :" k0300" }," $$" :[{" #name" :" text" ," _" :" ring aromatic Hy" },{" #name" :" keyword" ," $" :{" id" :" k0310" }," $$" :[{" #name" :" text" ," _" :" hydrophobic RMSF" },{" #name" :" keyword" ," $" :{" id" :" k0320" }," $$" :[{" #name" :" text" ," _" :" root mean square fluctuation RGyr" },{" #name" :" keyword" ," $" :{" id" :" k0330" }," $$" :[{" #name" :" text" ," _" :" radius of gyration binding free energy QSARINS" },{" #name" :" keyword" ," $" :{" id" :" k0350" }," $$" :[{" #name" :" text" ," _" :" QSAR-INSUBRIA |
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