Charged Thienobenzo-1,2,3-Triazoles as Especially Potent Non-Selective Cholinesterase Inhibitors: Design, Anti-Inflammatory Activity, and Computational Study
<b>Background/Objectives</b>: This research reports the synthesis and evaluation of novel charged thienobenzo-triazoles as non-selective cholinesterase inhibitors (AChEs and BChEs), their anti-inflammatory properties, and a computational study. <b>Methods</b>: Fifteen derivat...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
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| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/7/1032 |
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| Summary: | <b>Background/Objectives</b>: This research reports the synthesis and evaluation of novel charged thienobenzo-triazoles as non-selective cholinesterase inhibitors (AChEs and BChEs), their anti-inflammatory properties, and a computational study. <b>Methods</b>: Fifteen derivatives were created through photochemical cyclization and quaternization of the triazole core. The compounds were tested for AChE and BChE inhibition. They showed greater potency and selectivity toward BChE. <b>Results</b>: The most potent compound, derivative 14, inhibited BChE with an IC<sub>50</sub> of 98 nM, while derivative <b>9</b> also displayed significant anti-inflammatory activity by inhibiting LPS-induced TNF-α production (IC<sub>50</sub> = 0.66 µM). Molecular docking revealed that triazolinium salts form key π-π and electrostatic interactions within enzyme active sites. In silico predictions indicated favorable ADME-Tox properties for compounds <b>9</b> and <b>11</b>, including low mutagenicity and moderate CNS permeability. <b>Conclusions</b>: These findings highlight the potential of new charged triazolinium salts as peripherally selective cholinesterase inhibitors with additional anti-inflammatory potential. |
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| ISSN: | 1424-8247 |