Synthesis of novel thiosemicarbazone derivatives and investigation of their dual AChE and MAO-B inhibitor effects.

In this study, 15 thiosemicarbazone derivatives were synthesized. Analysis of the obtained compounds was performed by means of H-NMR, C-NMR and high resolution mass spectroscopy (HRMS) spectroscopic methods. The inhibition effect of the obtained compounds on cholinesterase and monoaminoxidase (MAO) enzymes were investigated with in vitro methods. None of the compounds showed significant activity on the butyrylcholinesterase enzyme. On the other hand, compounds 3b, 3c, 3e, 3k, 3l, 3m, 3n and 3o displayed significant activity on acetylcholinesterase (AChE) while compounds 3f, 3i, 3k, 3l, 3m, 3n, 3o also showed remarkable effects on monoamine oxidase-B (MAO-B) enzymes. For the selected compounds, docking studies were performed and the enzyme active site and binding modes were determined. It was revealed that the strongest interaction with AChE and MAO-B enzyme active sites was observed with the compound 3k. Another important factor in the treatment of diseases affecting the central nervous system such as Alzheimer's is the ability of the compounds to cross the blood-brain barrier (BBB). Additionally, the agents planned for the treatment of these diseases must also pass the blood-brain barrier. Therefore, in silico BBB penetration properties of active compounds were investigated.