| Titre : | A computational study of natural inhibitors as potential Anti - cancer Agents |
| Auteurs : | Zohra Saidane, Auteur ; Dalal Harkati, Directeur de thèse |
| Editeur : | Biskra [Algérie] : Faculté des Sciences Exactes et des Sciences de la Nature et de la Vie, Université Mohamed Khider, 2023 |
| Format : | 1 vol. (84 p.) / couv. ill. en coul / 30 cm |
| Langues: | Anglais |
| Langues originales: | Anglais |
| Mots-clés: | Computer-aided drug design, Estrogen receptor alpha (Erα), Breast cancer, Natural Compounds, Virtual screening, Lead compound, Molecular docking, ADMET, Chemical reactivity descriptor, Citrullus colocynthis, Cucurbitacines, flavonoids. |
| Résumé : |
Breast cancer stands as one of the most frequently diagnosed cancers among women, with a noteworthy 80% of cases being positive for Estrogen Receptor α (ERα). This receptor subtype holds significant therapeutic importance, prompting our study's focus on it. Selective estrogen receptor modulators (SERMs), such as tamoxifen, and selective estrogen receptor degraders (SERDs), such as fulvestrant, directly target ERα. To explore potential compounds, we turned to Citrullus colocynthis, which contains cucurbitacins and flavonoids. Through molecular docking, we accurately assessed their affinity to bind with ERα. Subsequently, we predicted the ADMET properties and chemical reactivity descriptors of these compounds. Our computational approach suggests that Cucurbitacine J and 2S-3',4'-methylene dioxy-5,7- dimethoxy flavan exhibit favorable inhibitory characteristics against the ERα receptor, providing an alternative pathway for understanding the binding mechanism of these compounds. |
| Sommaire : |
GENERAL INTRODUCTION ………………………1 CHAPTER I: LITERARY REVIEW 1 COMPUTER-AIDED DR.......... 5 1.2 MAJOR TYPES OF APPROACHES IN CADD ........... 7 1.2.1 Structure based drug design / direct ap.... 7 1.2.2 Legend based drug design / indirect approach ............ 8 1.3 VIRTUAL SCREE..................... 9 1.4 MOLECULAR DOCK................... 11 1.4.1 Typs of molecular docking ..... 12 1.4.1.1 Flexible Dock................ 12 1.4.1.2 Le docking semi-flexible .... 13 1.4.1.3 Rigid Docking ............... 13 1.4.2.1 Receptor .................... 13 1.6 CALCULATION OF HOMO AND LUMO ENERGIES ............ 20 1.7 EXAMPLES OF DRUGS SYNTHESIZED USING CADD ......... 21 1.8 SUCCESS AND LIMITATIONS........................... 22 2 AN OVERVIEW OF BREST CANCER ........................ 23 WHO IS MAINLY AFFECTED BY BREAST CANCER? ............. 24 2.1 MANAGEMENT OF BREAST CANCER ...................... 24 2.1.1 Surgery...........24 2.1.2 Radiation Therapy Radiation therapy ........ 24 2.1.3 Chemotherapy ............................... 25 2.1.4 Hormone therapy for breast cancer .......... 25 2.1.5 Hormone therapy for breast cancer ...........25 Erreur ! Signet non défini. 2.1.6 Cell-Target Suicide................ 25 3 ESTROGEN RECEPTOR ALPHA IN HUMAN BREAST CANCER................ 26 3.1 OCCURRENCE AND SIGNIFICANCE ......... 26 3.2 STRUCTURE ........................... 28 3.3 ROLES..................... 28 3.4 INVOLVED MECHANISMS................. 29 3.5 DRUGS THAT BLOCK ESTROGEN RECEPTORS. 30 3.5.1Selectiveestrogenreceptormodulators(SERMs).......... 30 3.5.2 Selective estrogen receptor degraders (SERDs)...... 30 CHAPTERⅡ : MATERIALS AND METHODS 1 GENERAL PROTOCOL...................... 36 2 COMPOUND COLLECTIONS ................. 37 3 CITRULLUS COLOCYNTHIS COLOCYNTH THE SOURCE OF CUCURBITACINS AND FLAVONOIDS ........... 37 3.1 STRUCTURE OF CUCURBITACINS ......... 38 3.2 STRUCTURS OF FLAVONOIDS............. 40 4 COMPUTUTIONAL DETAI................... 42 5.1 THE 2D AND 3D STRUCTU............... 42 5.2 RECEPTOR PREPARATION ............... 42 6 MOLECULAR DOCKING .................... 43 7 COMPUTATIONEL PHARMACOKINETICS ....... 43 8 OPTIMIZATION AND GLOBAL REACTIVITY CALCULATION ...... 44 CHAPTER III : RESULTS AND DISCUSSION 1 RESULTS AND DISCUSSION OF CUCURBITACINS COMPOUNDS ... 49 1.1 MOLECULAR DOCKING RESULTS ............................... 49 1.2 ADMET PROPERTIES OF CUCURBITACINS COMPOUNDS ............. 56 1.3 REACTIVITY .............................................. 58 2 RESULTS AND DISCUSSION OF FLAVONOIDS COMPOUNDS ............ 59 2.1 MOLECULAR DOCKING RESULTS ............................... 59 2.2 ADMET PROPRIETIES RESULTS ............................... 66 2.3 REACTIVITY OF FLAVONOIDS COMPOUNDS ...................... 68 |
| Type de document : | Mémoire master |
Disponibilité (1)
| Cote | Support | Localisation | Statut |
|---|---|---|---|
| MCH/610 | Mémoire master | bibliothèque sciences exactes | Consultable |
