Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors.

MAO-B inhibitors are frequently used in the treatment of neurodegenerative diseases such as Parkinson's and Alzheimer's. Due to the limited number of compounds available in this field, there is a need to develop new compounds. In the recent works, it was shown that various thiosemicarbazone derivatives show MAO inhibitory activity in the range of micromolar concentration. It is thought that benzofuran and benzothiophene structures may mimic structures such as indane and indanone, which are frequently found in the structures of such inhibitors. Based on this view, new benzofuran/benzothiophene and thiosemicarbazone hybrid compounds were synthesized, characterized and screened for their MAO-A and MAO-B inhibitory activity by an in vitro fluorometric method. The compounds including methoxyethyl substituent ( and ) were found to be the most effective agents in the series against MAO-B enzyme with the IC value of 0.042 ± 0.002 µM and 0.056 ± 0.002 µM, respectively. The mechanism of MAO-B inhibition of compounds and was investigated by Lineweaver-Burk graphics. Compounds and were reversible and non-competitive inhibitors with similar inhibition features as the substrates. The K values of compounds and were calculated as 0.035 µM and 0.046 µM, respectively, with the help of secondary plots. The docking study of compound and revealed that there is a strong interaction between the active sites of MAO-B and analyzed compound.