Investigation of the potential of being a drug candidate by examining the anti-cancer properties of some newly synthesized organic molecules

Within the scope of the TUBITAK project numbered 118Z187, 1,2,4-triazole skeleton and substituents that could be effective on hEGFR were designed by in-silico methods, and molecules were synthesized to be used in this thesis. Within the scope of the thesis, first of all, the optimum reaction conditions of the commercially purchased enzyme were determined. The optimum protein and substrate concentrations of the enzyme were calculate as 0,01 µg/mL and 0,5 mM, respectively. The IC50 value of each molecule was found by kinetic studies. Molecules with the best IC50 values were determined as 31 (0,0004 mM) and 9, 27, 30 (0,0008 mM). The inhibition types of molecules were investigated and the best Ki values of these molecules were calculated as 0,00232 µM (31) and 0,0889 µM (9). A549, NCI-H358, WI-38, OVCAR-3, SKOV-3 cells were used for biocompatibility tests of molecules (9, 27, 30, 31) with the best inhibitory effect. Molecules with the best cytotoxicity were found as 9 and 27. The activity of gefitinib and four molecules against the OVCAR-3 cell, and the activity of molecule 9 against the WI38 cell could not be determined. In ADME studies, it was predicted that none of the synthesized molecules had blood-brain barrier crossing properties, and most of them had passive gastrointestinal absorbtion properties. Keywords: hEGFR, Enzyme inhibition, ELISA, 1,2,4-triazole, Cytotoxicity, ADME