Delogu, Giovanna LuciaKumar, AmitGatto, GianlucaBustelo Paz, FernandoSaavedra, Lucía MRodríguez Franco, María IsabelLaguna-Francia, ReyesViña Castelao, María Dolores2024-02-092024-02-092021-01-05Delogu, G.L.; Kumar, A.; Gatto, G.; Bustelo, F.; Saavedra, L.M.; Rodríguez-Franco, M.I.; Laguna, R.; Viña, D. Synthesis and in vitro study of nitro- and methoxy-2-phenylbenzofurans as human monoamine oxidase inhibitors. Bioorg. Chem. 2021;107:1046161090-21200045-2068http://hdl.handle.net/10347/32623A new series of 2-phenylbenzofuran derivatives were designed and synthesized to determine relevant structural features for the MAO inhibitory activity and selectivity. Methoxy substituents were introduced in the 2-phenyl ring, whereas the benzofuran moiety was not substituted or substituted at the positions 5 or 7 with a nitro group. Substitution patterns on both the phenyl ring and the benzofuran moiety determine the affinity for MAO-A or MAO-B. The 2-(3-methoxyphenyl)-5-nitrobenzofuran 9 was the most potent MAO-B inhibitor (IC50 = 0.024 μM) identified in this series, whereas 7-nitro-2-phenylbenzofuran 7 was the most potent MAO-A inhibitor (IC50 = 0.168 μM), both acting as reversible inhibitors. The number and position of the methoxyl groups on the 2-phenyl ring, have an important influence on the inhibitory activity. Molecular docking studies confirmed the experimental results and highlighted the importance of key residues in enzyme inhibition.eng© 2021 Elsevier Inc. All rights reservedhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es2-PhenylbenzofuransMonoamine Oxidase InhibitorsDocking studies3209journal article10.1016/j.bioorg.2020.104616open access