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

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 mu M) identified in this series, whereas 7-nitro-2-phenylbenzofuran 7 was the most potent MAO-A inhibitor (IC50 = 0.168 mu M), 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.

Automated summary

A new series of 2-phenylbenzofuran derivatives were designed and synthesized to investigate their MAO inhibitory activity and selectivity. The presence of methoxy substituents in the 2-phenyl ring and nitro groups at positions 5 or 7 on the benzofuran moiety affected the affinity for MAO-A or MAO-B. Experimental results showed 2-(3-methoxyphenyl)-5-nitrobenzofuran 9 as the most potent MAO-B inhibitor and 7-nitro-2-phenylbenzofuran 7 as the most potent MAO-A inhibitor in this series, with methoxy groups on the 2-phenyl ring playing a key role in inhibitory activity.