具有新酚类分子的喹唑啉衍生物的合成:作为替代性多酚氧化酶抑制剂的体外和硅学评估

IF 2.2 4区 化学 Q2 Engineering Chemical Papers Pub Date : 2024-09-19 DOI:10.1007/s11696-024-03670-5
Cansu Öztürk, Feyzi Sinan Tokali, Aykut Öztekin, Erbay Kalay, Yalçın Karagöz, Mine Aksoy
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引用次数: 0

摘要

我们以良好的收率制备出了几种带有酚羟基的新型喹唑啉衍生物(2-7),并对其进行了生物活性筛选。利用 1H NMR、13C NMR、FTIR 和 HRMS 等光谱技术对所有标题化合物进行了表征。然后,对合成的喹唑啉衍生物的抗褐变作用进行了体外研究。计算得出分子 2-7 的 IC50 值分别为 0.085、1.145、0.106、6.86、0.52 和 7.07 µM。利用 Lineweaver-Burk 图计算出的 Ki 常数(即抑制剂与酶的结合常数)分别为 0.16 ± 0.0620、0.906 ± 0.3029、0.055 ± 0.0171、9.363 ± 2.5809、0.773 ± 0.3204、7.863 ± 1.9107 µM。在计算机辅助分析中,为了深入了解电化学特性,利用密度泛函理论对合成的化合物进行了理论分析。进行了分子对接研究和 MD 模拟,以确定可能的抑制剂与酶的结合相互作用。结果表明,所有化合物都与 Asn 112 和 Asn 414 形成了氢键,并与目标蛋白中的守门残基 Phe2 70 发生了 π-阳离子相互作用。MD 模拟表明,蛋白质-抑制剂复合物在模拟过程中保持稳定并形成大量氢键,这支持了纳米级抑制作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Synthesis of quinazoline derivatives with new phenolic moieties: in vitro and in silico evaluations as alternative polyphenol oxidase inhibitors

Several novel quinazoline derivatives bearing phenolic hydroxyl moiety (2–7) have been produced with good yields and screened for biological activities. All the title compounds were characterized using spectroscopic techniques such as 1H NMR, 13C NMR, FTIR, and HRMS. Then, the anti-browning effects of synthesized quinazoline derivatives were investigated in vitro. The IC50 values for molecules 2–7 were calculated as 0.085, 1.145, 0.106, 6.86, 0.52, 7.07 µM, respectively. Ki constants, which are inhibitory-enzyme binding constants, were calculated by using Lineweaver–Burk graphs as 0.16 ± 0.0620, 0.906 ± 0.3029, 0.055 ± 0.0171, 9.363 ± 2.5809, 0.773 ± 0.3204, 7.863 ± 1.9107 µM, respectively. In computer-aided analysis, to gain insights electrochemical properties, synthesized compounds were analysed theoretically by density functional theory. Molecular docking studies and MD simulations were performed to identify possible inhibitor-enzyme binding interactions. According to obtained results, all the compounds formed hydrogen bonds with Asn 112 and Asn 414, and showed π-cation interaction with Phe2 70, gatekeeper residue in target protein. Supporting the nm level inhibition, MD simulations indicate that protein-inhibitor complex maintain the stability and have high number of hydrogen bond formation during the simulation.

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来源期刊
Chemical Papers
Chemical Papers Chemical Engineering-General Chemical Engineering
CiteScore
3.30
自引率
4.50%
发文量
590
期刊介绍: Chemical Papers is a peer-reviewed, international journal devoted to basic and applied chemical research. It has a broad scope covering the chemical sciences, but favors interdisciplinary research and studies that bring chemistry together with other disciplines.
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