Photochemically Assisted Synthesis of Thienobenzotriazole-Based Dual Cholinesterase Inhibitors

Background: It has been shown previously that thienobenzo-1,2,3-triazoles exhibit very good selective inhibition toward butyrylcholinesterase (BChE), while the same derivatives converted into salts also display inhibitory activity against acetylcholinesterase (AChE), enzymes relevant to Alzheimer’s disease therapy. They show even better BChE inhibition potential than neutral analogs. Methods: This study presents the synthesis and biological evaluation of a novel series of charged thienobenzo-1,2,3-triazolinium salts (1–17) as inhibitors of AChE and BChE. The basic skeleton of the targeted compounds was synthesized via a photochemical method and subsequently converted into corresponding bromide salts. Their structures were confirmed using NMR and HRMS analyses. Results: In vitro testing showed that all synthesized compounds exhibit moderate to strong BChE inhibition and, to a lesser extent, AChE inhibition. Compounds 8 and 11 emerged as the most potent AChE inhibitors (IC50 ~ 2.6–3.2 µM), while compounds 1, 2, and 8 demonstrated excellent and selective BChE inhibition (IC50 ~ 0.3–0.4 µM), outperforming the reference drug galantamine. Anti-inflammatory evaluation revealed limited activity, with compound 17 slightly reducing LPS-induced TNF-α production at the highest tested concentration. Conclusions: These findings highlight the role of the electric charge and substituent type in modulating biological activity and confirm the therapeutic potential of these molecules as dual cholinesterase inhibitors for further development in neurodegenerative disease treatment.