| Titre : | In silico analysis of pyrazole derivatives applied to drug design |
| Auteurs : | Aouisset Darine, 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, 2022 |
| Format : | 1 vol. (92 p.) |
| Langues: | Anglais |
| Mots-clés: | cancer disease, biological activities, pyrazole, MPO, MLR, QSAR, docking, EGFR. |
| Résumé : |
The widespread use of the microscope in the 18th century led to the discovery of the cancer disease which remains to this day the deadliest of diseases. What has prompted most researchers and chemists to intensify the study on the discovery of new molecules to inhibit them. In this work, we studied a series of pyrazole derivatives. This occupies an important place in the pharmaceutical field because of the multiplicity of its biological activities. In this study, Lipophilic Efficacy (LipE), Lipinski and Veber of Multifactor Optimization (MPO) process was used to predict the best balance of properties of these compounds. The Multiple Linear Regression (MLR) method was also applied to derive the QSAR model .In silico molecular docking to present the interactions between the studied molecules and the enzyme (EGFR). |
| Sommaire : |
General Introduction Bibliographic references 1st part: bibliographic research Chapter I: Bibliographic review on 1, 2-diazoles and cancer disease I.1.Introduction I.2. 1,2-Diazole Core Chemical Appearance I.2.1 General I.2.2. Synthesis of 1,2-diazole I.3. biological activity of symdiazole derivatives I.4. Symdiazole as medicine I.5. Cancer and EGFR inhibitors for the treatment of cancer I.5.1. the cancer A. Generality B. Symptoms and consequences of cancer I.5.2. EGFR receptor I.5.3. EGFR protein inhibitors as anti-cancer agents I.6. Conclusion Bibliographic references Chapter II : Molecular modeling methods used in drug selection II.1.Introduction II.2. Representation of calculation methods II.2.1. Molecular Mechanics II.2.2. Quantum mechanics II.3. Quantitative structure-activity relationships (QSAR) II.3.1.Introduction II.3.2. Molecular Descriptors A. Physico-Chemical Descriptors B. Hydrophobicity Descripton II.3.3. Validation of QSAR Models II.3.4. Applications of the QSAR study II.4. Molecular Docking II.4.1. Introduction II.4.2. Scoring Fonctions II.5. Conclusion Bibliographic references 2nd part: Results and discussion Chapter III : Structural study, Electronics, MESP on the basic core: 1, 2-diazole, using several molecular and quantum mechanical calculation methods, and the experimental synthesis protocol III.1.Introduction III.2. Study of the basic core of 1,2-diazole III.3. Study of the effect of substitution on the pyrazole base core skeleton II.4. Synthesis of chalcone II.5. Synthesis of pyrazole III.6. Conclusion Bibliographic references Chapter IV: Qualitative study of the structure-activity relationship of a series of 1,2-diazole derivatives. IV.1.Introduction IV.2. Study of the QSAR properties of the series of pyrazole derivatives IV.2.1. Chemical structures of 1, 2-diazole derivatives IV.2.2. Study of the physico-chemical properties of pyrazole derivatives IV.3. QSAR theoretical and multi-parameter optimization (MPO) IV.3.1 Representation of “drug-like” calculations based on Lipinski IV.3.2. Veber’s rules IV.3.3. Efficiency of ligand "LE" IV.3.4. Ligand Lipophilicity Efficiency "LLE" IV.3.5. Golden triangle IV.4. Conclusion Bibliographic references Chapter V : Quantitative study of the QSAR properties of a series of 1,3,5-triazine derivatives and application of chemometric methods V.1. Introduction V.2. QSAR tools and techniques V.2.1. Biological parameters V.2.2. Molecular descriptors V.2.3 Multiple Linear Regression (MLR) A. Description of the method B. Testing the overall significance of the regression V.3. Quantitative studies on structure-activity relationships V.4. QSAR model development V.4.1- Results and discussion V.4.2- Quantification of descriptors V.5. Model validation V.6. Conclusion Bibliographic references Chapter VI : Study by molecular docking of the interactions between the EGFR enzyme and pyrazole derivatives VI.1.Introduction VI.2. drug discovery parameters VI.2.1. the RMSD (Root Meany Square Deviation) VI.2.2. Receptor-Ligand Interactions A. The hydrogen bond B. Van Der Waals interactions C. Hydrophobic interaction D. Ionic bonds VI.3. Preparation of receptor and ligands VI.3.1. Protein Preparation Structure VI.3.2. Preparation of the ligands VI.3.3.Cavity detection VI.4. Results and interpretations VI.4.1. Protein-ligand interactions VI.5. Conclusion Bibliographic references General conclusion |
Disponibilité (1)
| Cote | Support | Localisation | Statut |
|---|---|---|---|
| MCH/560 | Mémoire master | bibliothèque sciences exactes | Empruntable |
