Molecular Modeling of Antimalarial Agents by 3D-QSAR Study and Molecular Docking of Two Hybrids 4-Aminoquinoline-1,3,5-triazine and 4-Aminoquinoline-oxalamide Derivatives with the Receptor Protein in Its Both Wild and Mutant Types
Modeling studies using 3D-QSAR and molecular docking methods were performed on a set of 34 hybrids of 4-aminoquinoline derivatives previously studied as effective antimalarial agents of wild type and quadruple mutant Plasmodium falciparum dihydrofolate reductase (DHFR). So, the famous mathematical m...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Biochemistry Research International |
| Online Access: | http://dx.doi.org/10.1155/2018/8639173 |
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| author | Hanine Hadni Mohamed Mazigh El’mbarki Charif Asmae Bouayad Menana Elhallaoui |
| author_facet | Hanine Hadni Mohamed Mazigh El’mbarki Charif Asmae Bouayad Menana Elhallaoui |
| author_sort | Hanine Hadni |
| collection | DOAJ |
| description | Modeling studies using 3D-QSAR and molecular docking methods were performed on a set of 34 hybrids of 4-aminoquinoline derivatives previously studied as effective antimalarial agents of wild type and quadruple mutant Plasmodium falciparum dihydrofolate reductase (DHFR). So, the famous mathematical method multiple linear regression (MLR) was explored to build the QSAR model. The DFT-B3LYP method with the basis set 6-31G was used to calculate the quantum chemical descriptors, chosen to represent the electronic descriptors of molecular structures. On the contrary, the MM2 method was used to calculate lipophilic, geometrical, physicochemical, and steric descriptors. The QSAR model tested with artificial neural network (ANN) method shows high performance towards its predictability. The predicted model was confirmed by three validation methods: leave-one-out (LOO) cross validation, Y-randomization, and validation external. The molecular docking study of three compounds 9, 11, and 26 on both wild and quadruple mutant types of pf-DHFR-TS as the protein target helps to understand more and then predict the binding modes with the binding sites. |
| format | Article |
| id | doaj-art-e013ce99e08c40fdb80d1f99b3a58f25 |
| institution | Kabale University |
| issn | 2090-2247 2090-2255 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Biochemistry Research International |
| spelling | doaj-art-e013ce99e08c40fdb80d1f99b3a58f252025-02-03T05:59:54ZengWileyBiochemistry Research International2090-22472090-22552018-01-01201810.1155/2018/86391738639173Molecular Modeling of Antimalarial Agents by 3D-QSAR Study and Molecular Docking of Two Hybrids 4-Aminoquinoline-1,3,5-triazine and 4-Aminoquinoline-oxalamide Derivatives with the Receptor Protein in Its Both Wild and Mutant TypesHanine Hadni0Mohamed Mazigh1El’mbarki Charif2Asmae Bouayad3Menana Elhallaoui4Engineering Materials, Modeling and Environmental Laboratory, Faculty of Sciences of Dhar Elmehraz, Sidi Mohammed Ben Abdellah University, B.P. 1796, Atlas, Fes, MoroccoEngineering Materials, Modeling and Environmental Laboratory, Faculty of Sciences of Dhar Elmehraz, Sidi Mohammed Ben Abdellah University, B.P. 1796, Atlas, Fes, MoroccoEngineering Materials, Modeling and Environmental Laboratory, Faculty of Sciences of Dhar Elmehraz, Sidi Mohammed Ben Abdellah University, B.P. 1796, Atlas, Fes, MoroccoEngineering Materials, Modeling and Environmental Laboratory, Faculty of Sciences of Dhar Elmehraz, Sidi Mohammed Ben Abdellah University, B.P. 1796, Atlas, Fes, MoroccoEngineering Materials, Modeling and Environmental Laboratory, Faculty of Sciences of Dhar Elmehraz, Sidi Mohammed Ben Abdellah University, B.P. 1796, Atlas, Fes, MoroccoModeling studies using 3D-QSAR and molecular docking methods were performed on a set of 34 hybrids of 4-aminoquinoline derivatives previously studied as effective antimalarial agents of wild type and quadruple mutant Plasmodium falciparum dihydrofolate reductase (DHFR). So, the famous mathematical method multiple linear regression (MLR) was explored to build the QSAR model. The DFT-B3LYP method with the basis set 6-31G was used to calculate the quantum chemical descriptors, chosen to represent the electronic descriptors of molecular structures. On the contrary, the MM2 method was used to calculate lipophilic, geometrical, physicochemical, and steric descriptors. The QSAR model tested with artificial neural network (ANN) method shows high performance towards its predictability. The predicted model was confirmed by three validation methods: leave-one-out (LOO) cross validation, Y-randomization, and validation external. The molecular docking study of three compounds 9, 11, and 26 on both wild and quadruple mutant types of pf-DHFR-TS as the protein target helps to understand more and then predict the binding modes with the binding sites.http://dx.doi.org/10.1155/2018/8639173 |
| spellingShingle | Hanine Hadni Mohamed Mazigh El’mbarki Charif Asmae Bouayad Menana Elhallaoui Molecular Modeling of Antimalarial Agents by 3D-QSAR Study and Molecular Docking of Two Hybrids 4-Aminoquinoline-1,3,5-triazine and 4-Aminoquinoline-oxalamide Derivatives with the Receptor Protein in Its Both Wild and Mutant Types Biochemistry Research International |
| title | Molecular Modeling of Antimalarial Agents by 3D-QSAR Study and Molecular Docking of Two Hybrids 4-Aminoquinoline-1,3,5-triazine and 4-Aminoquinoline-oxalamide Derivatives with the Receptor Protein in Its Both Wild and Mutant Types |
| title_full | Molecular Modeling of Antimalarial Agents by 3D-QSAR Study and Molecular Docking of Two Hybrids 4-Aminoquinoline-1,3,5-triazine and 4-Aminoquinoline-oxalamide Derivatives with the Receptor Protein in Its Both Wild and Mutant Types |
| title_fullStr | Molecular Modeling of Antimalarial Agents by 3D-QSAR Study and Molecular Docking of Two Hybrids 4-Aminoquinoline-1,3,5-triazine and 4-Aminoquinoline-oxalamide Derivatives with the Receptor Protein in Its Both Wild and Mutant Types |
| title_full_unstemmed | Molecular Modeling of Antimalarial Agents by 3D-QSAR Study and Molecular Docking of Two Hybrids 4-Aminoquinoline-1,3,5-triazine and 4-Aminoquinoline-oxalamide Derivatives with the Receptor Protein in Its Both Wild and Mutant Types |
| title_short | Molecular Modeling of Antimalarial Agents by 3D-QSAR Study and Molecular Docking of Two Hybrids 4-Aminoquinoline-1,3,5-triazine and 4-Aminoquinoline-oxalamide Derivatives with the Receptor Protein in Its Both Wild and Mutant Types |
| title_sort | molecular modeling of antimalarial agents by 3d qsar study and molecular docking of two hybrids 4 aminoquinoline 1 3 5 triazine and 4 aminoquinoline oxalamide derivatives with the receptor protein in its both wild and mutant types |
| url | http://dx.doi.org/10.1155/2018/8639173 |
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