Charged Thienobenzo-1,2,3-Triazoles as Especially Potent Non-Selective Cholinesterase Inhibitors: Design,...

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Pharmacology

Background:

• Research focuses on developing novel thienobenzo-triazoles.
• Investigating their potential as cholinesterase inhibitors and anti-inflammatory agents.

Purpose of the Study:

• Synthesize and evaluate new charged thienobenzo-triazoles.
• Assess their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).
• Explore their anti-inflammatory properties and computational profiles.

Main Methods:

• Photochemical cyclization and quaternization to create 15 derivatives.
• In vitro assays for AChE and BChE inhibition.
• Molecular docking and in silico ADME-Tox predictions.

Main Results:

• Compounds exhibited higher potency and selectivity for BChE inhibition.
• Derivative 14 showed potent BChE inhibition (IC50 = 98 nM).
• Derivative 9 demonstrated anti-inflammatory activity, inhibiting TNF-α production (IC50 = 0.66 µM).
• Favorable ADME-Tox properties predicted for derivatives 9 and 11.

Conclusions:

• Novel charged triazolinium salts are effective cholinesterase inhibitors.
• These compounds display potential as peripherally selective BChE inhibitors.
• The derivatives possess dual cholinesterase inhibitory and anti-inflammatory properties.