The synthesis and biological activity studies of new chalcones and hydrazones deriving from 4-morpholinoacetophenone

Cancer is one of the most important diseases of our age and according to the records of International World Research Fund, more than 14 million patients got cancer in 2012. Designing new medication is needed because resistance has been developed for the current drugs used in cancer treatment and the drugs have significant side-effects. For this purpose using 4'-morpholine acetophenone as the starting compound, chalcone derivatives (1-13) and hydrazone derivatives (14-35) were synthesized and their structures were identified with techniques such as elemental analysis (CHNS), IR, 1H NMR, 13C NMR, 19F NMR, HETCOR, HSQC, HMBC, COSY, TOF-MS and LC-MS. The anticancer activities of the synthesized compounds were tested C6 and HeLa cell cultures compared to the reference drug, 5-fluorouracile (5-FU). The results showed that compound 3 (IC50 12.80 µg/mL) and compound 6 (IC50 4.16 µg/mL) had cell selectivity for C6 cell. In addition, the carbonic anhydrase I (CAI), carbonic anhydrase II (CAII) and pyruvate kinase M2 (PKM2) enzyme activities of these new compunds were evaluated. Twenty compounds showed inhibition effect against CA I enzyme. The compound 16 had the highest inhibition effect with a value of 45 µM IC50. Coumpound 8 activated PKM2 enzyme with a very low AC50 value of 2.20 µM. Keywords: chalcone, hydrazone, anticancer activity, hCA I and II, PKM2