Promising Non-cytotoxic Monosubstituted Chalcones to Target Monoamine Oxidase‑B
A library of monosubstituted chalcones (1–17) bearing electron-donating and electron-withdrawing groups on both aromatic rings were selected. The cell viability on human tumor cell lines was evaluated first. The compounds unable to induce detectable cytotoxicity (1, 13, and 14) were tested using the...
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| Veröffentlicht in: | ACS medicinal chemistry letters 2021-07, Vol.12 (7), p.1151-1158 |
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| container_title | ACS medicinal chemistry letters |
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| creator | Iacovino, Luca G Pinzi, Luca Facchetti, Giorgio Bortolini, Beatrice Christodoulou, Michael S Binda, Claudia Rastelli, Giulio Rimoldi, Isabella Passarella, Daniele Di Paolo, Maria Luisa Dalla Via, Lisa |
| description | A library of monosubstituted chalcones (1–17) bearing electron-donating and electron-withdrawing groups on both aromatic rings were selected. The cell viability on human tumor cell lines was evaluated first. The compounds unable to induce detectable cytotoxicity (1, 13, and 14) were tested using the monoamine oxidase (MAO) activity assay. Interestingly, they inhibit MAO-B, acting as competitive inhibitors, with 13 and 14 showing the best profiles. In particular, 13 exhibited a potency higher than that of safinamide, taken as a reference. Docking studies and crystallographic analysis showed that in human MAO-B 13 binds with the halogen-substituted aromatic ring in the entrance cavity, similar to safinamide, whereas 14 is accommodated in the opposite way. The main conclusion of this cell biology, biochemistry, and structural study is to highlights 13 as a chalcone derivative that is worth consideration for the development of novel MAO-B-selective inhibitors for the treatment of neurodegenerative diseases. |
| doi_str_mv | 10.1021/acsmedchemlett.1c00238 |
| format | Article |
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The cell viability on human tumor cell lines was evaluated first. The compounds unable to induce detectable cytotoxicity (1, 13, and 14) were tested using the monoamine oxidase (MAO) activity assay. Interestingly, they inhibit MAO-B, acting as competitive inhibitors, with 13 and 14 showing the best profiles. In particular, 13 exhibited a potency higher than that of safinamide, taken as a reference. Docking studies and crystallographic analysis showed that in human MAO-B 13 binds with the halogen-substituted aromatic ring in the entrance cavity, similar to safinamide, whereas 14 is accommodated in the opposite way. The main conclusion of this cell biology, biochemistry, and structural study is to highlights 13 as a chalcone derivative that is worth consideration for the development of novel MAO-B-selective inhibitors for the treatment of neurodegenerative diseases.</description><identifier>ISSN: 1948-5875</identifier><identifier>EISSN: 1948-5875</identifier><identifier>DOI: 10.1021/acsmedchemlett.1c00238</identifier><identifier>PMID: 34262643</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Letter</subject><ispartof>ACS medicinal chemistry letters, 2021-07, Vol.12 (7), p.1151-1158</ispartof><rights>2021 The Authors. Published by American Chemical Society</rights><rights>2021 The Authors. Published by American Chemical Society.</rights><rights>2021 The Authors. 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Chem. Lett</addtitle><description>A library of monosubstituted chalcones (1–17) bearing electron-donating and electron-withdrawing groups on both aromatic rings were selected. The cell viability on human tumor cell lines was evaluated first. The compounds unable to induce detectable cytotoxicity (1, 13, and 14) were tested using the monoamine oxidase (MAO) activity assay. Interestingly, they inhibit MAO-B, acting as competitive inhibitors, with 13 and 14 showing the best profiles. In particular, 13 exhibited a potency higher than that of safinamide, taken as a reference. Docking studies and crystallographic analysis showed that in human MAO-B 13 binds with the halogen-substituted aromatic ring in the entrance cavity, similar to safinamide, whereas 14 is accommodated in the opposite way. 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| subjects | Letter |
| title | Promising Non-cytotoxic Monosubstituted Chalcones to Target Monoamine Oxidase‑B |
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