Design, synthesis and investigation of biological activities of new kinase inhibitors with anti-cancer effect

Cancer is a disease whose incidence increases every year, especially with changing new living conditions, and unfortunately, 20% of people who are diagnosed lose their lives. Radical treatment is not yet possible in cancer therapy with conventional chemotherapeutics, and today small inhibitor molecules and monoclonal antibodies are important groups that stand out for radical treatment. Among the small inhibitor molecules are kinase inhibitors, which are involved in every point of signal transmission and inhibit protein kinases that can be easily inhibited. Across the field of this thesis, 20 new compounds with thiadiazole structure were synthesized based on the alpelisib molecule. In the synthesized compounds, the bioisostere benzene ring was used as an equivalent to the pyridine ring found in the modeled compound, and derivatives containing different substituents were used to observe modifications that may affect the activity.In addition, since it is known that combined treatments are more effective in cancer therapy, it has been tried to design compounds that can dual inhibit EGFR-COX-2 by adding sulfonamide substitution to some compounds. The synthesis of the compounds was done in coincidence with the literature and the structures of the compounds have been confirmed using IR, 1H-NMR, 13C-NMR and HRMS spectral analysis methods. To measure anticancer activity, A549 and MCF-7 cell lines were used and tests were performed in-vitro. For 3j and 3o compounds, advanced activity studies and molecular placement and molecular dynamics studies were performed then the inhibition potentials of EGFR and COX-2 were investigated.