| Titre : | Design and selection of new heterocyclic molecules of medical interest by in silico methods. |
| Auteurs : | Seridji, Auteur ; Salah Belaidi, Directeur de thèse |
| Type de document : | Monographie imprimée |
| Editeur : | Biskra [Algérie] : Faculté des Sciences Exactes et des Sciences de la Nature et de la Vie, Université Mohamed Khider, 2023 |
| Format : | 1vol(85) |
| Langues: | Français |
| Mots-clés: | 1H-1,2,3-triazole , DFT , SAR , MPO , QSAR, MLR, ANN. |
| Résumé : |
The purpose of this work carried out during this memory concerns a fundamental and novel research which aims to discuss and predict the activity of a series of thirty two derivatives of 1H-1,2,3-triazole which can be antioxidants.
In the first step of this research work, different theoretical calculation methods (MP2 and DFT/B3LYP) were used to study the basic core and validate a method to calculate the structures of the series of 1H-1,2,3-triazoles.We found that the DFT/B3LYP method was the most appropriate, so this method was used to determine the structural, electronic parameters associated with the molecules studied. Then, a qualitative structure-activity relationship (SAR) study was also performed for this bioactive series of 1H-1,2,3-triazole derivatives using different MPO methods. Finally, a quantitative study was also carried out to predict the biological activity of the studied compounds and its derivatives by suggesting the best QSAR model by means of the method of multiple linear regression (MLR) and the method of artificial neural networks (ANN), which are used to quantify the relationships between molecular descriptors and antioxidant activity. |
| Sommaire : |
Chapter I: General information on stress oxidative and antioxidants activity
I.1. Introduction: .......... 4 I.2. Oxidative stress:....... 4 I .2.1. Reactive species: ........... 5 I .2.1.1. Reactive oxygen species: ........... 6 I .2.1.2. Reactive nitrogen species: ........... 7 I.2.2. Consequences of oxidative stress: ........ 7 I .2.2.1. DNA oxidative damage: .............. 7 I .2.2.2. Lipid peroxidation: ............... 8 I .2.2.3. Protein oxidation: .............. 8 I .2.3. Oxidative stress diseases: ............. 9 I .2.3.1. Type 2 diabetes: ..................... 9 I .2.3.2. Inflammation: ..................... 9 I .2.3.3. Atherosclerosis: ................ 10 I. 2.3.4. Cancer: .................. 10 I.3. Antioxidants: ............10 I .3.1. Definition:............. 10 I.3.2. Enzymatic antioxidant systems: ...... 11 I.3.2.1. Catalase: ............ 11 I.3.2.2. Glutathione peroxidase: ..... 11 I.3.2.3. The dismutase superoxide: ....... 12 I.3.3. Non-enzymatic: ................ 13 I.3.3.1. Vitamins:.................. 13 I.3.3.2. Oligo-elements: ...........14 I.3.3.3. Polyphenols: ........... 15 Table of contents I.3.4. Methods of quantification of antioxidant activity: ........... 15 References............ 17 Chapter II: Computational approaches for drug design and discovery II.1. Introduction: ................... 20 II.2. Computer-aided drug design basic principles: ............. 20 II.2.1. Molecular mechanics: .............. 20 II.2.2. Quantum mechanics: ............. 22 II.2.3. Drug-likenes rules for drug discovery: .... 23 II.2.4. Quantitative structure-activity relationships (QSAR): ...... 24 II.2.4.1. Introduction: ............ 2 II.2.4.2. The data to model: ............ 25 II.2.4.3. QSAR properties that characterize the molecular structure: ............ 25 II.2.4.4. Statistical methods used in QSAR analysis: ...................... 27 II.2.4.5. Testing the overall significance of the regression: ........ 29 II.2.4.6. Validation of QSAR Models:........ 30 II.2.4.7. Evaluation of the model:.......... 32 II.2.4.8. Applications of the QSAR study: .............. 33 II.3. Conclusion: .......... 33 References......... 34 2ndpart: Results and discussion Chapter III: Structural study, Electronics, MESP on the basic core using several molecular and quantum mechanical calculation methods III.1. Introduction: ................. 38 III.2. Study of the structural and electronic properties of the basic core of 1H-1,2,3-triazole: 39 III.3. Molecular electrostatic potential: .......... 43 III.4. Conclusion:......... 45 References: ................ 46 Chapter IV: Qualitative study of the structure-activity relationship of a series of 1H-1, 2, 3-triazole derivatives IV.1. Introduction: ....... 47 Table of contents IV.2. Study of the QSAR properties of the series of 1H-1,2,3-triazole derivatives: ................. 47 IV.2.1. Chemical structures of 1H-1,2,3-triazole derivatives: ......... 47 IV.2.2. Study of the physico-chemical properties of 1H-1,2,3-triazole derivatives:......................... 52 IV.3. Drug like and multi-parameter optimization (MPO):.............. 54 IV.3.1. Representation of “drug-like” calculations based on Lipinski: ............... 54 IV.3.2. Veber’s rules: ............... 57 IV.3.3. Efficiency of ligand "LE": ............. 58 IV.3.4. Ligand Lipophilicity Efficiency "LLE": .............. 60 IV.3.5. Golden Triangle:.............. 62 IV.4. Calculation of Padel descriptors : ......... 64 IV.5. Conclusion: ......... 65 References............. 67 Chapter V: Quantitative structure-activity relationship (QSAR) of a series of 1H-1,2,3-triazole derivatives and application of chemometric methods V.1. Introduction : ......... 69 V.2. Quantitative study of the structure-activity relationship: ..... 70 V.2.1. Multiple Linear Regression (MLR): ........... 72 V.2.1.1. QSAR model development: ............. 72 V.2.1.2. Validation of the QSAR model:....... 74 V.2.2. Artificial neural networks : .............. 78 V.3. Identification of leads: ........ 81 V.4. Conclusion: .................. 82 References............. 83 General conclusion……………………………………………………………85 |
Disponibilité (1)
| Cote | Support | Localisation | Statut |
|---|---|---|---|
| MCH/647 | Mémoire master | bibliothèque sciences exactes | Consultable |
