Indole-based thiosemicarbazones for neurodegenerative diseases as prolyl oligopeptidase inhibitors

One of the highly expressed enzymes in the brain, prolyl specific oligopeptidase (POP), is a key target for the treatment of illnesses of the central nervous system including, autism spectrum, schizophrenia, Parkinson 's, dementia, and Alzheimer 's. In the current studies we report a series of indole based thiosemicarbazone as prolyl oligopeptidase (POP) inhibitors. Numerous approaches, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and mass-spectrometry (MS) procedures, were used to confirm the structures of all substances. These compounds were evaluated against POP interestingly all these tested molecules significantly inhibit POP in vitro at very low doses (5.74 -25.30 mu M). Compound 3g displayed the highest inhibition with IC 50 value 5.74 +/- 0.27 mu M. Kinetic studies of compounds, 3g, revealed concentration dependent type of inhibition with Ki value 4.31 +/- 0.0012 mu M. Furthermore, molecular docking was also performed to understand the binding modes of compounds, which correlates with our in vitro outcomes.