Thiol bearing aryl Schiff bases of 2-aminothiophenol as acetylcholinesterase and butyrylcholinesterase inhibitors

Abstract The diverse biological activities of Schiff bases in numerous industrial, pharmacological and medical domains pave the way for the development of phenol-derived Schiff bases as anti-Alzheimer’s agents. Different substituted thiol-bearing Schiff base derivatives 3(a–i) was synthesised and analyzed via different spectroscopic analysis such as FT-IR, 1 H-NMR, 13 C-NMR, & HR-EIMS. To ascertain their anti-Alzheimer potential, these derivatives undergo systematic screening against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. In contrast to tacrine, a well-established drug with IC 50 values of 47.0 ± 1.5 nM for AChE and 43.1 ± 1.3 nM for BChE, Schiff base analogues illustrated varied inhibitory potential having IC 50 concentrations ranging from 4.1 ± 0.3 to 41.1 ± 0.1 nM (AChE) and 7.1 ± 0.2 to 39.0 ± 0.2 nM (BChE), even suppressing the well-known drug. The most promising of these synthetic compounds was analogue 3i , which possesses an acetoxy moiety at the benzene ring para position. The effectiveness of this candidate was demonstrated through the acetoxy group’s participation in hydrogen bonding interactions with the targeted enzyme’s active regions. Molecular docking was also employed to investigate potential drug binding interactions with targeted enzymes and analogue reactivity. We discovered a strong correlation between in vitro productivity and in silico research.