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含不同芳基乙酰肼的氯苯基喹唑啉-4(3H)-酮的合理设计、合成、体外和计算机模拟研究作为酪氨酸酶抑制剂。

Rational Design, Synthesis, in Vitro, and in Silico Studies of Chlorophenylquinazolin-4(3H)-One Containing Different Aryl Acetohydrazides as Tyrosinase Inhibitors.

机构信息

CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran.

School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran.

出版信息

Chem Biodivers. 2022 Jul;19(7):e202100964. doi: 10.1002/cbdv.202100964. Epub 2022 Jun 8.

Abstract

Tyrosinase plays a pivotal role in the hyperpigmentation and enzymatic browning of fruit and vegetable. Therefore, tyrosinase inhibitors can be of interest in industries as depigmentation compounds as well as anti-browning agents. In the present study, a series of chlorophenylquinazolin-4(3H)-one derivative were rationally designed and synthesized. The formation of target compounds was confirmed by spectral characterization techniques such as IR, H-NMR, C-NMR, and elemental analysis. Among the synthesized derivatives, compound 8l was proved to be the most potent inhibitor with an IC value of 25.48±1.19 μM. Furthermore, the results of the molecular docking study showed that this compound fitted well in the active site of tyrosinase with the binding score of -10.72.

摘要

酪氨酸酶在水果和蔬菜的过度色素沉着和酶促褐变中起着关键作用。因此,酪氨酸酶抑制剂可以作为脱色化合物和抗褐变剂在工业中引起关注。在本研究中,合理设计并合成了一系列氯代苯并喹唑啉-4(3H)-酮衍生物。通过光谱特征技术,如 IR、H-NMR、C-NMR 和元素分析,确认了目标化合物的形成。在所合成的衍生物中,化合物 8l 被证明是最有效的抑制剂,IC 值为 25.48±1.19 μM。此外,分子对接研究的结果表明,该化合物与酪氨酸酶的活性位点结合良好,结合评分为-10.72。

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