Abstract

A series of ethyl 2-amino-4H-benzo[h]chromene-3-carboxylate derivatives, having phenyl ring with diverse substituents at C₄ position of 4H-benzochromene nucleus, were synthesized via one-pot three-component reaction between various aromatic aldehydes, α-naphthol, and ethyl cyanoacetate. The synthesized compounds were screened for their antityrosinase activity. Compound 4i, bearing 4-dimethylamino substitution on C₄-phenyl ring, was the most potent tyrosinase inhibitor (IC₅₀ = 34.12 μM). The inhibition kinetic analysis of 4i indicated that the compound was a competitive tyrosinase inhibitor. Compounds 4a, 4g, 4i and 4j were the effective radical scavengers with EC₅₀s in the range of 0.144–0.943 mM. According to the in silico drug-like and ADME predictions, 4i can be considered as a suitable candidate. Molecular docking results confirmed that the derivative was well accommodated within the mushroom tyrosinase binding site. Therefore, 4i can be introduced as a novel tyrosinase inhibitor that might be a promising lead in medicine, cosmetics, and food industry.

Graphic abstract

中文翻译：

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4H-苯并色烯衍生物作为新型酪氨酸酶抑制剂和自由基清除剂：合成、生物学评价和分子对接分析。

 抽象的

通过一锅三组分反应合成了一系列在4H-苯并色烯核C ₄位具有不同取代基的苯环的2-氨基-4H-苯并[h]色烯-3-甲酸乙酯衍生物。各种芳香醛、 α-萘酚、氰基乙酸乙酯。筛选合成的化合物的抗酪氨酸酶活性。化合物4i在C ₄ -苯环上带有4-二甲氨基取代基，是最有效的酪氨酸酶抑制剂(IC ₅₀ = 34.12 μM)。 4i的抑制动力学分析表明该化合物是一种竞争性酪氨酸酶抑制剂。化合物4a 、 4g 、 4i和4j是有效的自由基清除剂，EC ₅₀ s 在 0.144–0.943 mM 范围内。根据计算机模拟药物和 ADME 预测， 4i可以被视为合适的候选者。分子对接结果证实该衍生物很好地容纳在蘑菇酪氨酸酶结合位点内。因此， 4i可以作为一种新型酪氨酸酶抑制剂引入，在医药、化妆品和食品工业中可能具有广阔的应用前景。

 图文摘要