| Titre : | Structure-based discovery of novel Cyclin Dependent Kinase 2 inhibitors for the treatment of cancer |
| Auteurs : | Menatallah Khadidja KHALDI, Auteur ; Saida Khamouli , Directeur de thèse |
| Editeur : | Biskra [Algérie] : Faculté des Sciences Exactes et des Sciences de la Nature et de la Vie, Université Mohamed Khider, 2024 |
| Format : | 1 vol. (71 p.) / ill., couv. ill. en coul / 30 cm |
| Langues: | Anglais |
| Langues originales: | Anglais |
| Résumé : |
Cyclin-dependent kinase inhibition is considered a promising target for cancer treatment for its crucial role in cell cycle regulation. In this work, we are focused on the development of new potential inhibitors Cyclin-dependent kinase 2 in order to enrich the therapeutic classes of anticancer drugs.Molecular docking studies were applied to investigate the binding mode of the promising compounds and CDK2 receptor by calculating their docking energies and visualizing their interaction with active site of CDK-2 protein compared to the crystalized ligand. The ADME studies and drug-likeness showed proper pharmacokinetic properties which helped in structure requirements prediction for the observed antitumor activity. The in-silico results allowed us to conclude that ligands: L5, L23, and L24 could be a potential inhibitor of the Cyclin-dependent kinase 2. |
| Sommaire : |
Introduction...2 CHAPTER I: Overview of cancer disease and cyclin- dependent kinase 2...4 I.1 Introduction...6 I.2 Definition...6 I.3 Differences between Cancer Cells and Normal Cells...8 I.4 types of cancer...9 I.4.1 Epithelial and Blood Cell Cancers...9 I.4.2 Connective Tissue and Nervous System Cancers...9 I.5 Epidemiology...10 I.6 Cancer Causes...11 I.7 The stages of cancer...11 I.8 Symptoms...13 I.9 Early detection...13 I.10 Treatment...14 I.11 Cyclin dependent kinase 2 inhibitors (CDK2)...20 I.11.1 Definition of Cyclin-Dependent Kinases (CDK)...20 I.11.2 Cyclin-dependent kinases regulation Cell Cycle...21 I.11.3 Cyclin-dependent Kinases' Target Proteins...22 I.12.The Purines...23 I.12.1 Definition...23 I.12.2 Biological activities of purine analogue...23 Chapiter II: Computational Methods in Drug Discovery...25 II.1. Drug discovery...28 II.2. Steps in Modern Drug Discovery...29 II.3. Virtual Screening...34 II.3.1. Ligand-based Virtual Screening...34 II.3.1.1 Similarity Search...35 II.3.1.2 Ligand-based Pharmacophore Models...35 II.3.1.3 Quantitative Structure-Activity Relationship (QSAR)...36 II.3.2 Structure-Based Virtual Screening...36 II.3.2.1 Structure-Based Pharmacophore...37 II.3.2.2 .1 General Principle of Molecular Docking...37 II.3.2.2 .2 Types of Molecular Docking...38 II.3.2.2 .3 Search Algorithms...39 II.3.2.2 .4 Scoring Process...40 II.4. ADME-TOX...42 II.4. 1 Drug likeness...42 II.4.2 Pharmacokinetic and Toxicity Properties...42 II.4.2.1 Absorption...42 II.4.2.2 Distribution...42 II.4.2.3 Metabolism...43 II.4.2.4 Excretion...43 II.4.2.5 Toxicity...43 Chapiter III : Molecular docking and ADME study of 6- substituted 2- arylaminopurine derivative as anticancer agents...44 III.2. Materials and Methods...48 III.2.1. Computer System and Software...48 III.2.2 Methodology of calculations...50 III.3.2.1. Dataset...50 III.3.2.2. Ligand preparation...50 III.3.2.3. Protein preparation...56 III.3.2.4. Generation of Receptor Grid...57 III.3.2.5. Molecular docking...57 III.3.2.6. In silico ADME prediction...58 III.4. Results and discussions...60 III.4.1. Molecular Docking...60 III.4.2. Drug likeness and ADME prediction...67 III.4.2.1 Drug likeness...67 III.4.2.2 ADME prediction...69 References...72 Conclusion...75 |
| Type de document : | Mémoire master |
Disponibilité (1)
| Cote | Support | Localisation | Statut |
|---|---|---|---|
| MCH/629 | Mémoire master | bibliothèque sciences exactes | Consultable |
