| Titre : | In silico study of natural products as potential lead compounds in drug discovery |
| Auteurs : | KHALED abderaouf, Auteur ; Dalal Harkati, 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. (79 p.) |
| Langues: | Anglais |
| Mots-clés: | Computational drug design, Molecular optimization, Virtual screening, Lead compound, Molecular docking, in silico screening, EGFR inhibitors. |
| Résumé : |
The term drug design describes the systematic search for new compounds with biological activity. Understanding the drug design process is necessary for the development of new drugs and their clinical applications to alleviate modern epidemic diseases. Explain the principles of drug design in the pharmaceutical industry based on targets and selected ligands using molecular docking, pharmacophore modeling, and virtual screening methods. Computational drug design (CADD) is a specialized field that uses computational knowledge-based methods to aid the drug discovery process. The calculation method is estimated to save up to 2-3 years and $300 million. Chemoinformatics enables researchers to perform virtual screening to select lead compounds for synthesis and screening. This enables scientists to make quick decisions on lead compound identification and optimization. Researchers can use in silico ADMET modeling to find a bioavailable drug with suitable drug metabolism properties. The development of selective protein kinase inhibitors that can block or modulate diseases in which these signaling pathways are abnormal is considered a promising approach for drug development. Therefore, the goal of this research is to use computational approaches (virtual screening, Molecular optimization, Molecular docking, and ADMET properties) to explore and identify novel active agents that can act as EGFR inhibitors from five selected molecules: thymoquinone, diosgenin, protodioscin, trigonelline, and Ladanein. |
| Sommaire : |
Acknowledgments ..... i Abstract .......... ii Keyword.......... iii Table of Contents ....... iv List of Figures ........ viii List of Tables ........ viii List of Abbreviations .....ix General Introduction ..... 2 Chapter I: Literature review Introduction ............ 4 I.1 Topic 1: COMPUTER-AIDED DRUG DESIGN ..... 5 I.1.1 What is a drug? .......... 5 I.1.2 Computer-aided drug design ......... 5 I.1.3 The most common approaches on CADD ...... 6 I.1.4 Virtual Screening ........... 9 I.1.5 Molecular Docking and Scoring ............ 10 I.1.6 In silico ADMET............. 10 I.1.7 The roles of CADD in drug discov 11 I.2 Topic 2: PROTEIN KINASES AS TARGETS FOR ANTICANCER AGENTS.11 I.2.1 Cell structure .... 12 I.2.2 Types of Drug targets ..... 13 I.2.3 Role of the Receptor ........ 14 I.2.4 The Protein-tyrosine Kinases Receptor (RTKs) ........ 15 I.2.5 Structure of tyrosine kinase receptors ................ 16 I.2.6 Activation mechanism for tyrosine kinase receptors ........ 17 I.2.7 The EGFRs Subtypes and ligands ........ 17 I.2.8 EGFR (ERBB1) ....... 18 References ....... 21 Chapter II: Materials and methods Introduction ............. 25 II.1 COMPOUND COLLECTIONS ......... 27 v II.2 COMPUTATIONAL DETAILS ...... 29 II.3 MOLECULE LIBRARY PREPARATION .......... 29 II.3.1 The 2D and 3D structures ......... 29 II.3.2 Optimization and global reactivity calculations ......... 29 II.3.3 ADME properties ........... 31 II.4 RECEPTOR PREPARATION ....... 33 II.5 MOLECULAR DOCKING ............ 35 References .......... 36 Chapter III: Results and discussion III.1 THE OPTIMIZATION AND GEOMETRIC STRUCTURE......... 40 III.2 ELECTRONIC PROPERTIES ........... 42 III.2.1Frontier Molecular Orbitals (FMO) ........ 42 III.2.2Molecular Electrostatic Potential (MEP) ......... 45 III.3 REACTIVITY ANALYSIS.......... 50 III.3.1 Global Reactivity Descriptors .......... 50 III.3.2 Local Reactivity Descriptors ............ 52 III.4 ADMET PROPERTIES .......................... 59 III.5 MOLECULAR DOCKING STUDIES ................... 61 Conclusions ........... 74 References ...... 75 Appendices……………………77 |
Disponibilité (1)
| Cote | Support | Localisation | Statut |
|---|---|---|---|
| MCH/545 | Mémoire master | bibliothèque sciences exactes | Empruntable |
