"Computer-aided design and synthesis of new 4,6- disubstituted quinazoline derivatives having potential anticancer activity"

Abstract

Cancer is a medical term include group of diseases characterized by abnormal cell growth of uncontrolled division and which have the ability to invade tissues and destroy normal body tissues. It can spread all over the body at which the cells grow very rapidly forming malignant tumors that can transfer to different tissues through blood vessels and lymphatics. As cancer cells are derived from normal ones most traditional therapies affect targets that present in both types of cells. 4-Anilinoquinazoline derivatives have been designed and its interaction energy and binding with EGFR enzyme has been studied, compounds of good results has been synthesized and evaluated as anticancer agents against MCF-7 breast cancer cell line. Also some of these compounds (VIb, VIc, VIq, VIs, VIj, VIv, VIx, XIIIa, XIIIb, XIIIc, XIIId) have been evaluated against EGFR enzyme. The thesis compromise six chapters: 1. The introduction: This part describes cancer causes, discusses novel literature survey about its treatments and explains the different used mechanisms for designing different anticancer agents, this part gives a focus on EGFR inhibitors and clinically approved drugs by FDA. 2. Rational and design: Designing of new 4-anilinoquinazolines derivatives depending on the structure activity relationship and the essential groups for activity, also doking studies and binding energy scoring that gave best results for being synthesized according to scheme I,II 3. Results and discussion: 3.1. Molecular modeling It includes doking scores of hit compounds and its interaction energy calculations, as well as the binding modes inside EGFR enzyme binding site. Abstract xiv 3.2. Chemistry: This part includes all methods of synthesis the reported known and new compounds, synthesis of proposed compounds according to schemes I,II. All of synthesized compounds have been proved by different analytical and spectral data. 3.3. Biological evaluation All designed compounds are evaluated as anticancer agent against MCF-7 breast cancer cell line, some of them evaluated for its %inhibition against EGFR enzyme. 4. Conclusion: Based on the biological evaluation some of the hit compounds can be used for elucidation and designing of some new compounds as potent anticancer agents. 5. Experimental: 5.1. Molecular modeling Includes the procedure taken for calculation of doking the compounds in the enzyme and its binding energy calculation