Details

Autor(en) / Beteiligte

• Delogu, Giovanna L.
• Kumar, Amit
• Gatto, Gianluca
• Bustelo, Fernando
• Saavedra, Lucía M.
• Rodríguez-Franco, Maria Isabel
• Laguna, Reyes
• Viña, Dolores

Titel

Synthesis and in vitro study of nitro- and methoxy-2-phenylbenzofurans as human monoamine oxidase inhibitors

Ist Teil von

• Bioorganic chemistry, 2021-02, Vol.107, p.104616-104616, Article 104616

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• [Display omitted] •A series of nitro- and methoxy-2-phenylbenzofuran was synthesized.•Compounds displayed activity against monoamine oxidase enzymes.•Relevance of number/position of methoxyl substitution in enzyme activity.•Importance of nitro substitution in MAO-A enzyme activity.•Physicochemical properties are suitable for good bioavailability.•Docking studies assisted in explaining the structure-activity relationship. A 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.