| Titre : | Study of the structure, QSAR properties and molecular docking of some amino-pyrimidine derivatives as Novel Mycobacterium tuberculosis inhibitors for drug design |
| Auteurs : | Saida Khamouli , Auteur ; Salah Belaidi, Auteur |
| Type de document : | Thése doctorat |
| Editeur : | Biskra [Algérie] : Faculté des Sciences Exactes et des Sciences de la Nature et de la Vie, Université Mohamed Khider, 2019 |
| Format : | 1 vol. (98 p.) / 30 cm |
| Langues: | Anglais |
| Langues originales: | Anglais |
| Mots-clés: | anti-tuberculosis,CADD,MPO,MLR,QSAR,docking,ADMET. |
| Résumé : |
The discovery of anti-tuberculosis agents is crucial for effective tuberculosis therapy. The present strategy for new drug development is directed towards identifying essential enzyme systems in the bacteria and developing potent molecules to inhibit them.We have study the inhibition of 29 amino-pyrimidine derivatives of Mycobacterium tuberculosis PKnB using different CADD approaches to search for potential drug candidates. The multi-parameter optimization (MPO) process to predict the best balance of properties of these compounds was expressed by various approaches such as Lipophilic Efficiency (LipE), Lipinski, Veber rules. The Multiple linear regression method (MLR) was applied to derive QSAR model which was further validated for statistical significance by internal and external validation. In Silico molecular docking and ADMET properties used to predict novel PKnB inhibitors and guide the discovery of new potential analogs. |
| Sommaire : |
LIST OF FIGURES LIST OF TABLES LIST OF ABBREVIATIONS General Introduction CHAPTER I: The disease of tuberculosis 1. Tuberculosis 1.1 Introduction 1.2 TB Pathogenesis 1.3 Symptoms 1.4 Treatment and Prevention of Tuberculosis 1.4.1 Treatment of Tuberculosis 1.4.2 Mechanisms of Drug Resistance 1.4.3 Prevention of the Tuberculosis 2. Mycobacterium tuberculosis 2.1 General Characteristics 2.2 Taxonomy 2.3 Classification 2.4 Morphology 2.5 Cell-wall 3. Serine/threonine protein kinases (STPKs) 5. Challenges in the Development of New Drugs Reference CHAPTER II: Computational methods in drug discovery Introduction 2. Computer-aided drug design 2.1 Introduction 2.2 CADD applications in drug discovery and development 2.3 Classification of CADD 2.3.1 Ligand-based drug design (LBDD) 2.3.2 Structure-based drug discovery (SBDD 2.4 Molecular mechanics 2.5 Quantum mechanics 3. Quantitative structure-activity relationships (QSAR 3.1 Introduction 3.2 History of QSAR 3.3 Tools and Techniques of QSAR 3.3.1 Biological Parameters 3.3.2 Molecular Descriptors 3.3.3 Statistical methods 3.3.4 Multiple linear regressions (MLR 3.4 Validation of QSAR Models 3.4.1 Internal Validation 3.4.2 External validation 4. Molecular Docking 4.1 Introduction 4.2 Search Algorithms 4.3 Scoring functions Reference CHAPTER III: Qualitative Structure-Activity Relationships and 2D-QSAR Modeling of PKnB Inhibition by Amino-pyrimidines Derivatives Introduction 2 Materials and methods 2.1 Data Set 2.2 Molecular descriptors 2.3 Model validation 3 Results and discussion 3.1 Structure Activity Relationship (SAR) and drug likeness 3.2 Quantitative Structure-Activity Relationships Studies 3.2.1 Internal validation 3.2.2 External Validation Conclusion Reference CHAPTER III: In silico Molecular docking and ADMET study of amino-pyrimidine derivatives as mycobacterium tuberculosis PKnB Introduction 2 Material and methods 2.1 Protein Preparation Structure 2.2 Ligands structure optimization 2.3 Molecular Docking 2.4 Drug Likeness and Pharmacokinetic Properties of selected ligands 3 Results and discussion 3.1 Validation of Model structures 3.2 Prediction of binding sites 3.3 Protein-Ligand Docking 3.4 Drug-likeness and ADMET Properties of selected ligands 3.4.1 Drug-likeness of selected ligands 3.4.2 ADMET study of selected ligands Conclusion Reference General Conclusion |
| Type de document : | Thése doctorat |
| En ligne : | http://thesis.univ-biskra.dz/id/eprint/4720 |
Disponibilité (1)
| Cote | Support | Localisation | Statut |
|---|---|---|---|
| TCH/76 | Théses de doctorat | bibliothèque sciences exactes | Consultable |
