School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran.
Department of Chemistry, Payam Noor University, Tehran, Iran.
Bioorg Chem. 2022 Sep;126:105876. doi: 10.1016/j.bioorg.2022.105876. Epub 2022 May 16.
In the present study, a series of 3-hydroxy-1H-pyrrol-2(5H)-one derivative were rationally designed and synthesized. The structure of targeted compounds was confirmed by IR, H NMR, C NMR, and elemental analysis. Next, all derivatives were evaluated as tyrosinase inhibitors, and among the synthesized derivatives, compound 6a was proved to be the most potent inhibitor with an IC value of 6.98 ± 1.05 µM. Kinetic study of compound 6a confirmed the mixed type of inhibitory activity towards tyrosinase. Furthermore, the results of the molecular docking study showed that this compound fitted well in the active site of tyrosinase and exhibited interaction with important residues of the binding site.
在本研究中，我们合理设计并合成了一系列 3-羟基-1H-吡咯-2(5H)-酮衍生物。目标化合物的结构通过红外光谱（IR）、核磁共振氢谱（H NMR）、核磁共振碳谱（C NMR）和元素分析得到确认。接下来，我们评估了所有衍生物作为酪氨酸酶抑制剂的活性，在合成的衍生物中，化合物 6a 被证明是最有效的抑制剂，其 IC 值为 6.98±1.05µM。化合物 6a 的动力学研究证实了其对酪氨酸酶的混合抑制活性。此外，分子对接研究的结果表明，该化合物能够很好地适应酪氨酸酶的活性部位，并与结合部位的重要残基发生相互作用。
