Charged Thienobenzo-1,2, 3-Triazoles as Especially Potent Non-Selective Cholinesterase Inhibitors: Design, Anti-Inflammatory Activity and Computational Study

This study presents the synthesis and evaluation of novel charged thienoben-zo-1,2,3-triazoles as non-selective cholinesterase inhibitors (AChE and BChE), including their anti-inflammatory properties and computational analysis. Fifteen derivatives were synthesized via photochemical cyclization and triazole core quaternization. The compounds were tested for AChE and BChE inhibition, showing greater potency and selectivity toward BChE. The most potent compound, derivative 14, inhibited BChE with an IC₅₀ of 98 nM, while derivative 9 also demonstrated significant anti-inflammatory activity by inhibiting LPS-induced TNF-α production (IC₅₀ = 0.66 µM). Molecular docking revealed that triazolium salts form key π-π and electrostatic interactions within enzyme active sites. In silico predictions indicated favorable ADME-Tox properties for compounds 9 and 11, including low mutagenicity and moderate CNS permeability. These results highlight the potential of novel charged triazoles as peripherally selective cholinesterase inhibitors with added anti-inflammatory effects.