Investigation of in silico anticancer potential of selected natural products potent modulators of epidermal growth factor receptor

Cancer can be shortly described as a disorder in multicellular organisms in which some of the cells grow abnormally and spread to other organs of the body called metastasis. It can embark on almost any tissue in the human body. Normally, human cells grow and multiply by means of tightly controlled cell division to generate new cells as the body requires them. Actually, metastasis makes up the main cause of death for approximately more than >90% of patients with cancer. Drug discovery dates back to the ancient times of human civilization. Historically, treatments and/or new medicines were generally discovered by chance or through observation of their therapeutic effect on disease phenotypes, either directly in humans or in models of disease. However, modern drug discovery research depends on pre-clinical (basic research) and clinical trials and includes expensive and complicated processes. Natural products are a great group of secondary metabolites produced by living organisms to optimize nature. Natural sources such as terrestrial higher plants, fungi, bacteria, and marine organisms synthesize the metabolites to adapt the their microenvironments. To date, many FDA approved drugs have been discovered for therapeutic use from natural sources, including Taxol (paclitaxel), vincristine/vinblastine (anticancer), fingolimod (multiple sclerosis), cyclosporine and doxorubicin (immunosuppressant). Nowadays, naturally occurring compounds are a great reservoir for drug discovery and design. In this MSc thesis, we have focused on potential modulatory activities of triterpenoid-based natural products and their derivatives by Click Chemistry towards epidermal growth factor receptor (EGFR) protein through computed-aided screening. Our findings revealed that azole derivatives of betulinic acid and ursolic acid showed significantly binding affinity on EGFR protein by molecular docking