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 mu M against (AChE) and 0.30 +/- 0.1 to 37.60 +/- 0.6 mu M against (BChE) enzymes. Among the series compounds 8 (IC50 = 0.17 +/- 0.05 mu M) (IC50 = 0.30 +/- 0.1 mu M), 9 (IC50 = 0.30 +/- 0.05 mu M) (IC50 = 0.60 +/- 0.05 mu M) and 10 (IC50 = 1.30 +/- 0.1 mu M) (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 H-1 NMR, C-13 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.

Automated summary

Indole-based thiadiazole derivatives were synthesized and evaluated for their inhibition of AChE and BChE. Compounds with para, ortho, and meta-fluoro substitutions on the phenyl ring attached to thiadiazole showed the highest activity. Characterization was done using NMR, MS, and molecular docking studies were conducted.