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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2025-04-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Mariagrazia Rullo |
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| description | 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). |
| format | Article |
| id | doaj-art-d77d2dd8ed7e491185f418b72e5ccefb |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-04-01 |
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| series | Molecules |
| spelling | doaj-art-d77d2dd8ed7e491185f418b72e5ccefb2025-08-20T02:28:32ZengMDPI AGMolecules1420-30492025-04-01308183010.3390/molecules30081830In Vitro Evaluation of Novel Furo[3,2-<i>c</i>]coumarins as Cholinesterases and Monoamine Oxidases InhibitorsMariagrazia Rullo0Alice Benzi1Lara Bianchi2Massimo Maccagno3Guglielmo Marcantoni Taddei4Daniela Valeria Miniero5Giuseppe Felice Mangiatordi6Giovanni Lentini7Leonardo Pisani8Giovanni Petrillo9Cinzia Tavani10Department of Pharmacy—Pharmaceutical Sciences, University of Bari “Aldo Moro”, Via E. Orabona, 4, 70125 Bari, ItalyDepartment of Chemistry and Industrial Chemistry (DCCI), University of Genova, Via Dodecaneso 31, 16146 Genova, ItalyDepartment of Chemistry and Industrial Chemistry (DCCI), University of Genova, Via Dodecaneso 31, 16146 Genova, ItalyDepartment of Chemistry and Industrial Chemistry (DCCI), University of Genova, Via Dodecaneso 31, 16146 Genova, ItalyDepartment of Chemistry and Industrial Chemistry (DCCI), University of Genova, Via Dodecaneso 31, 16146 Genova, ItalyDepartment of Medicine & Surgery, LUM University Giuseppe Degennaro Torre Rossi, 70010 Puglia, ItalyCNR, Institute of Crystallography, 70126 Bari, ItalyDepartment of Pharmacy—Pharmaceutical Sciences, University of Bari “Aldo Moro”, Via E. Orabona, 4, 70125 Bari, ItalyDepartment of Pharmacy—Pharmaceutical Sciences, University of Bari “Aldo Moro”, Via E. Orabona, 4, 70125 Bari, ItalyDepartment of Chemistry and Industrial Chemistry (DCCI), University of Genova, Via Dodecaneso 31, 16146 Genova, ItalyDepartment of Chemistry and Industrial Chemistry (DCCI), University of Genova, Via Dodecaneso 31, 16146 Genova, ItalyCoumarin 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).https://www.mdpi.com/1420-3049/30/8/1830furo[3,2-<i>c</i>]coumarinsacetylcholinesterasebutyrylcholinesterasemonoamine oxidasesdocking simulationsenzyme inhibitors |
| spellingShingle | 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 In Vitro Evaluation of Novel Furo[3,2-<i>c</i>]coumarins as Cholinesterases and Monoamine Oxidases Inhibitors Molecules furo[3,2-<i>c</i>]coumarins acetylcholinesterase butyrylcholinesterase monoamine oxidases docking simulations enzyme inhibitors |
| title | In Vitro Evaluation of Novel Furo[3,2-<i>c</i>]coumarins as Cholinesterases and Monoamine Oxidases Inhibitors |
| title_full | In Vitro Evaluation of Novel Furo[3,2-<i>c</i>]coumarins as Cholinesterases and Monoamine Oxidases Inhibitors |
| title_fullStr | In Vitro Evaluation of Novel Furo[3,2-<i>c</i>]coumarins as Cholinesterases and Monoamine Oxidases Inhibitors |
| title_full_unstemmed | In Vitro Evaluation of Novel Furo[3,2-<i>c</i>]coumarins as Cholinesterases and Monoamine Oxidases Inhibitors |
| title_short | In Vitro Evaluation of Novel Furo[3,2-<i>c</i>]coumarins as Cholinesterases and Monoamine Oxidases Inhibitors |
| title_sort | in vitro evaluation of novel furo 3 2 i c i coumarins as cholinesterases and monoamine oxidases inhibitors |
| topic | furo[3,2-<i>c</i>]coumarins acetylcholinesterase butyrylcholinesterase monoamine oxidases docking simulations enzyme inhibitors |
| url | https://www.mdpi.com/1420-3049/30/8/1830 |
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