Synthesis of new 2-hydrazinothiazole derivatives and investigation of their biological effects

Alzheimer's and Parkinson's Diseases are neurodegenerative diseases and are becoming more common. There is currently no radical cure for Alzheimer's or Parkinson's disease. Clinically used drugs aim only for symptomatic relief and cannot stop neurodegeneration. One of the strategies commonly used in treatment of these diseases is to restore neurotransmitter levels by inhibiting cholinesterase (ChE) and monoamine oxidase (MAO) enzymes. In this thesis, 2-[2-(substituted benzylidene)hydrazinyl]-4-(substituted phenyl)thiazole derivatives (2a-2h) were synthesized by combining the hydrazine in the structure of monoamine oxidase inhibitor molecules and the thiazole ring, which is reported to have inhibitory activity against acetylcholinesterase and monoamine oxidase enzymes. The structures of the synthesized compounds were confirmed by 1H-NMR, 13C-NMR and mass spectroscopy. When the enzyme inhibition activities were evaluated, it was determined that compounds 2c, 2d and 2h showed the highest inhibitory activity against AChE, while compounds 2f and 2h showed the highest activity against MAO-B. It was determined that compound 2h had the highest inhibitory activity on both AChE (0.030±0.001 µM) and MAO-B (0.048±0.002 µM), and compound 2h was the only compound with dual inhibitory activity. The effects of the compounds on butyrylcholinesterase (BChE) and MAO-A enzymes could not be determined. All compounds were found to satisfy Lipinski's rule of five and additionally the results of the enzyme activity and the results of the docking study were found to be in agreement.