We herein report the biological evaluation of 3‐arylcoumarin derivatives (3a‐l) as potential human monoamine oxidase‐A and ‐B (hMAO‐A and hMAO‐B) inhibitors. The result indicated that 7,8‐dihydroxy‐3‐(4‐nitrophenyl)coumarin (3j) was most effective against MAO‐A (inhibition concentration [IC₅₀] = 6.46 ± 0.02 µM) and MAO‐B (IC₅₀ = 3.8 ± 0.3 µM) enzymes than other synthesized compounds and reference compounds (pargyline and moclobemide). Furthermore, compound (3j) showed (a) nonselectivity against hMAO enzymes, (b) reversible hMAO enzymes inhibition, and (c) neuroprotection against H₂O₂‐treated human neuroblastoma (N2a) cells. Finally, a molecular modeling study revealed that the hMAO enzymes inhibitory activity of the compound (3j) may be due to the orientation where the nitro (NO₂) group lies deep into the receptor and the phenyl ring directed toward flavin adenosine dinucleotide via hydrogen bond interaction, and possible π‐π interaction with various important residues. Thus, the results of the present study demonstrate that compound (3j) can be considered as a promising scaffold for the development of hMAO‐A and hMAO‐B inhibitors.

中文翻译：

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鉴定7,8-二羟基-3-苯基香豆素为可逆的单胺氧化酶抑制剂

我们在此报告了3-芳基香豆素衍生物（3a-1）作为潜在的人单胺氧化酶A和B（h MAO-A和h MAO-B）抑制剂的生物学评估。结果表明7,8-二羟基-3-（4-硝基苯基）香豆素（3j）对MAO-A（抑制浓度[IC ₅₀ ] = 6.46±0.02 µM）和MAO-B（IC ₅₀  = 3.8 ）最有效±0.3 µM）酶比其他合成化合物和参考化合物（Pargyline和Moclobemide）高。此外，化合物（3J）显示（a）打击nonselectivity ħ MAO酶，（b）中可逆ħ MAO酶抑制，和（c）针对ħ神经保护₂O ₂处理的人类神经母细胞瘤（N2a）细胞。最后，分子模型研究表明，化合物（3j）的h MAO酶抑制活性可能是由于硝基（NO ₂）基团深入受体和苯环通过氢指向黄素腺苷二核苷酸的取向键相互作用以及可能与各种重要残基的π-π相互作用。因此，本研究的结果表明，化合物（3j）可被视为开发h MAO-A和h MAO-B抑制剂的有前途的支架。