Exploring indole-based-thiadiazole derivatives as potent acetylcholinesterase and butyrylcholinesterase enzyme inhibitors.

Indole based thiadiazole derivatives (1-18) were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The IC values of the synthesized analogues ranging between 0.17 ± 0.05 to 33.10 ± 0.6 μM against (AChE) and 0.30 ± 0.1 to 37.60 ± 0.6 μM against (BChE) enzymes. Among the series compounds 8 (IC = 0.17 ± 0.05 μM) (IC = 0.30 ± 0.1 μM), 9 (IC = 0.30 ± 0.05 μM) (IC = 0.60 ± 0.05 μM) and 10 (IC = 1.30 ± 0.1 μM) (IC = 2.60 ± 0.1) were found to be the most potent analogues bearing para, ortho, and meta-fluoro substitutions on phenyl ring attached to thiadiazole. In addition, all the synthesized scaffolds were characterized by using H NMR, C NMR spectroscopy, and high-resolution Mass Spectrometry (HR-MS). To apprehend the binding mode of interaction of the most potent synthesized derivatives, a molecular docking study was performed.