In Vitro Evaluation of Novel Furo[3,2-<i>c</i>]coumarins as Cholinesterases and Monoamine Oxidases Inhibitors

Coumarin represents a privileged structural motif that is quite common in nature-derived and synthetic bioactive molecules. Some of us have recently described the straightforward preparation of complex furo[3,2-<i>c</i>]coumarins through a sequential double coupling protocol. Aiming at f...

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Main Authors: Mariagrazia Rullo, Alice Benzi, Lara Bianchi, Massimo Maccagno, Guglielmo Marcantoni Taddei, Daniela Valeria Miniero, Giuseppe Felice Mangiatordi, Giovanni Lentini, Leonardo Pisani, Giovanni Petrillo, Cinzia Tavani
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/8/1830
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Summary:Coumarin represents a privileged structural motif that is quite common in nature-derived and synthetic bioactive molecules. Some of us have recently described the straightforward preparation of complex furo[3,2-<i>c</i>]coumarins through a sequential double coupling protocol. Aiming at finding novel chemical probes for the modulation of key anti-Alzheimer’s targets, a small subset of furo[3,2-<i>c</i>]coumarin prototypes and their non-aromatic synthetic precursors were tested in vitro as inhibitors of ChEs (acetyl- and butyrylcholinesterase, AChE and BChE) and MAOs (monoamine oxidases A and B, MAO A and MAO B). All compounds were low-micromolar AChE inhibitors devoid of toxic effects against SH-SY5Y cells. Lineweaver-Burk plots and docking simulations suggested mixed-type kinetics for inhibitor <b>3d</b> (IC<sub>50</sub> = 4.1 μM toward AChE). Its promising inhibitory profile encompasses additional, highly selective, activity against monoamine oxidase B, with a submicromolar IC<sub>50</sub> value (561 nM).
ISSN:1420-3049