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 IC50 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 (IC50 = 0.17 ± 0.05 μM) (IC50 = 0.30 ± 0.1 μM), 9 (IC50 = 0.30 ± 0.05 μM) (IC50 = 0.60 ± 0.05 μM) and 10 (IC50 = 1.30 ± 0.1 μM) (IC50 = 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 1H NMR, 13C 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.