الفهرس | Only 14 pages are availabe for public view |
Abstract The present Thesis compromises the following chapters: Chapter 1 (Introduction and literature review ):an introduction describing cancer disease, its management, the role of BcL-2(Bcell lymphoma-2) family in cancer management and its inhibitors . Chapter 2 (Scientific Rationale) :it describes how new drug targeting BcL-2 protein can be designed Chapter 3 (Results and Discussion): a correlation between the chemical structures of novel compounds and obtained biological activities, molecular docking studies, summery and conclusion. Chapter 4 (experimental procedure):the present investigation involves the synthesis of 14 final compounds References : a list of references which were used and their management according to their order in the thesis Appendix: C13NMR and ,or H1NMR of all the compounds of this work. Apoptosis is a process of cellular suicide through which unwanted or unhealthy cells are eliminated during organism development or cellular stress. Deregulated apoptosis is a characteristic of cancer cells. The B-cell lymphoma-2 (Bcl-2) family plays pivotal role in the mitochondrial pathway of apoptosis by promoting the release of cytochrome c and Second mitochondrial-derived activator of caspases ( Smac) into the cytosol, resulting in caspase-dependent cell death. In most tumor tissues and cancer cell lines, the anti-apoptotic Bcl-2 proteins are frequently highly expressed. For example, Bcl-2 is overexpressed in prostate cancer, breast cancer, B-cell lymphomas, colorectal cancer. Therefore, developing potential inhibitors was an important target to prove the significance of Bcl-2 in cancer recovery process. In the present work, two schemes were designed, and new final compounds were synthesized. Based on the suggested scaffolds, straightforward and convenient synthetic chemical pathways were conducted as well as complete structural elucidation of the obtained compounds was performed using 1H-NMR, 13C-NMR, Mass spectrometry and elemental analysis. Concerning biological analysis, the synthesized compounds were evaluated using breast cancer, human lung adenocarcinoma, and non-malignant cell lines. Finally, molecular docking studies have been adopted to examine the predicted binding mode for these final compounds and obtain a greater insight through establishing SAR analysis correlating the compound chemical structures and their in-vitro biological activities. |