Hybrids of Methylxanthines and Azoderivatives as Acetylcholinesterase Inhibitors: Structure–Activity Relationship Analysis

In this work, we synthesized methylxanthine and azobenzene derivatives, linked to secondary amines via a seven-carbon chain, to evaluate their acetylcholinesterase (AChE) inhibitory activity. Among the azobenzene compounds, <b>3a</b> exhibited the highest activity with an IC<sub>50...

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Main Authors: Brunella Biscussi, Santiago Gundin, Martina Donozo, Ana Paula Murray
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Chemistry Proceedings
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Online Access:https://www.mdpi.com/2673-4583/16/1/111
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author Brunella Biscussi
Santiago Gundin
Martina Donozo
Ana Paula Murray
author_facet Brunella Biscussi
Santiago Gundin
Martina Donozo
Ana Paula Murray
author_sort Brunella Biscussi
collection DOAJ
description In this work, we synthesized methylxanthine and azobenzene derivatives, linked to secondary amines via a seven-carbon chain, to evaluate their acetylcholinesterase (AChE) inhibitory activity. Among the azobenzene compounds, <b>3a</b> exhibited the highest activity with an IC<sub>50</sub> of 1.1 µM. Meanwhile, the theobromine derivative <b>2a</b> was the most potent inhibitor among the methylxanthines, with an IC<sub>50</sub> of 0.19 µM. These results highlight the importance of structure–activity relationship analysis to optimize AChE inhibition by modifying pharmacophore fragments and secondary amines.
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spelling doaj-art-bca2dd896f0b488b932b0e2800ae481e2025-08-20T02:24:19ZengMDPI AGChemistry Proceedings2673-45832024-11-0116111110.3390/ecsoc-28-20258Hybrids of Methylxanthines and Azoderivatives as Acetylcholinesterase Inhibitors: Structure–Activity Relationship AnalysisBrunella Biscussi0Santiago Gundin1Martina Donozo2Ana Paula Murray3Departamento de Química, Instituto de Química del Sur (INQUISUR-CONICET-UNS), Universidad Nacional del Sur, Av. Alem 1253, Bahía Blanca 8000, ArgentinaDepartamento de Química, Instituto de Química del Sur (INQUISUR-CONICET-UNS), Universidad Nacional del Sur, Av. Alem 1253, Bahía Blanca 8000, ArgentinaDepartamento de Química, Instituto de Química del Sur (INQUISUR-CONICET-UNS), Universidad Nacional del Sur, Av. Alem 1253, Bahía Blanca 8000, ArgentinaDepartamento de Química, Instituto de Química del Sur (INQUISUR-CONICET-UNS), Universidad Nacional del Sur, Av. Alem 1253, Bahía Blanca 8000, ArgentinaIn this work, we synthesized methylxanthine and azobenzene derivatives, linked to secondary amines via a seven-carbon chain, to evaluate their acetylcholinesterase (AChE) inhibitory activity. Among the azobenzene compounds, <b>3a</b> exhibited the highest activity with an IC<sub>50</sub> of 1.1 µM. Meanwhile, the theobromine derivative <b>2a</b> was the most potent inhibitor among the methylxanthines, with an IC<sub>50</sub> of 0.19 µM. These results highlight the importance of structure–activity relationship analysis to optimize AChE inhibition by modifying pharmacophore fragments and secondary amines.https://www.mdpi.com/2673-4583/16/1/111acetylcholinesterase inhibitorsmicrowave-assisted synthesiscaffeine derivativesazobenzene derivatives
spellingShingle Brunella Biscussi
Santiago Gundin
Martina Donozo
Ana Paula Murray
Hybrids of Methylxanthines and Azoderivatives as Acetylcholinesterase Inhibitors: Structure–Activity Relationship Analysis
Chemistry Proceedings
acetylcholinesterase inhibitors
microwave-assisted synthesis
caffeine derivatives
azobenzene derivatives
title Hybrids of Methylxanthines and Azoderivatives as Acetylcholinesterase Inhibitors: Structure–Activity Relationship Analysis
title_full Hybrids of Methylxanthines and Azoderivatives as Acetylcholinesterase Inhibitors: Structure–Activity Relationship Analysis
title_fullStr Hybrids of Methylxanthines and Azoderivatives as Acetylcholinesterase Inhibitors: Structure–Activity Relationship Analysis
title_full_unstemmed Hybrids of Methylxanthines and Azoderivatives as Acetylcholinesterase Inhibitors: Structure–Activity Relationship Analysis
title_short Hybrids of Methylxanthines and Azoderivatives as Acetylcholinesterase Inhibitors: Structure–Activity Relationship Analysis
title_sort hybrids of methylxanthines and azoderivatives as acetylcholinesterase inhibitors structure activity relationship analysis
topic acetylcholinesterase inhibitors
microwave-assisted synthesis
caffeine derivatives
azobenzene derivatives
url https://www.mdpi.com/2673-4583/16/1/111
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