A structural approach to investigate halogen substituted MAO-B inhibitors using QSAR modeling, molecular dynamics, and conceptual DFT analysis
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-07-01
|
| Series: | Journal of Saudi Chemical Society |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319610323000790 |
| _version_ | 1797737381210619904 |
|---|---|
| author | Naseer Maliyakkal Iqrar Ahmad Sunil Kumar Sachithra Thazhathuveedu Sudevan Asmy Appadath Beeran Harun Patel Hoon Kim Bijo Mathew |
| author_facet | Naseer Maliyakkal Iqrar Ahmad Sunil Kumar Sachithra Thazhathuveedu Sudevan Asmy Appadath Beeran Harun Patel Hoon Kim Bijo Mathew |
| author_sort | Naseer Maliyakkal |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T13:27:52Z |
| format | Article |
| id | doaj.art-d51b598ab9aa492f824707cf6280822a |
| institution | Directory Open Access Journal |
| issn | 1319-6103 |
| language | English |
| last_indexed | 2024-03-12T13:27:52Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Saudi Chemical Society |
| spelling | doaj.art-d51b598ab9aa492f824707cf6280822a2023-08-25T04:23:51ZengElsevierJournal of Saudi Chemical Society1319-61032023-07-01274101675A structural approach to investigate halogen substituted MAO-B inhibitors using QSAR modeling, molecular dynamics, and conceptual DFT analysisNaseer Maliyakkal0Iqrar Ahmad1Sunil Kumar2Sachithra Thazhathuveedu Sudevan3Asmy Appadath Beeran4Harun Patel5Hoon Kim6Bijo Mathew7Department of Basic Medical Sciences, College of Applied Medical Sciences in Khamis Mushait, King Khalid University, Abha, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Prof. Ravindra Nikam College of Pharmacy, Gondur, Dhule 424002, Maharashtra, India; Division of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, IndiaDepartment of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, IndiaDepartment of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, IndiaManipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, IndiaDivision of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, IndiaDepartment of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of KoreaDepartment of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, India; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S1319610323000790Monoamine oxidase-BHalogenQSARMolecular dynamicPharmacophore modellingDensity functional theory |
| spellingShingle | Naseer Maliyakkal Iqrar Ahmad Sunil Kumar Sachithra Thazhathuveedu Sudevan Asmy Appadath Beeran Harun Patel Hoon Kim Bijo Mathew A structural approach to investigate halogen substituted MAO-B inhibitors using QSAR modeling, molecular dynamics, and conceptual DFT analysis Journal of Saudi Chemical Society Monoamine oxidase-B Halogen QSAR Molecular dynamic Pharmacophore modelling Density functional theory |
| title | A structural approach to investigate halogen substituted MAO-B inhibitors using QSAR modeling, molecular dynamics, and conceptual DFT analysis |
| title_full | A structural approach to investigate halogen substituted MAO-B inhibitors using QSAR modeling, molecular dynamics, and conceptual DFT analysis |
| title_fullStr | A structural approach to investigate halogen substituted MAO-B inhibitors using QSAR modeling, molecular dynamics, and conceptual DFT analysis |
| title_full_unstemmed | A structural approach to investigate halogen substituted MAO-B inhibitors using QSAR modeling, molecular dynamics, and conceptual DFT analysis |
| title_short | A structural approach to investigate halogen substituted MAO-B inhibitors using QSAR modeling, molecular dynamics, and conceptual DFT analysis |
| title_sort | structural approach to investigate halogen substituted mao b inhibitors using qsar modeling molecular dynamics and conceptual dft analysis |
| topic | Monoamine oxidase-B Halogen QSAR Molecular dynamic Pharmacophore modelling Density functional theory |
| url | http://www.sciencedirect.com/science/article/pii/S1319610323000790 |
| work_keys_str_mv | AT naseermaliyakkal astructuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT iqrarahmad astructuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT sunilkumar astructuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT sachithrathazhathuveedusudevan astructuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT asmyappadathbeeran astructuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT harunpatel astructuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT hoonkim astructuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT bijomathew astructuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT naseermaliyakkal structuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT iqrarahmad structuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT sunilkumar structuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT sachithrathazhathuveedusudevan structuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT asmyappadathbeeran structuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT harunpatel structuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT hoonkim structuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis AT bijomathew structuralapproachtoinvestigatehalogensubstitutedmaobinhibitorsusingqsarmodelingmoleculardynamicsandconceptualdftanalysis |