Abstract
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.
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