针对表皮生长因子受体的黄酮-查尔酮衍生物的分子对接和分子动力学研究,用于新型抗癌剂的初步发现

IF 1 Q4 CHEMISTRY, MULTIDISCIPLINARY
Y. S. Kurniawan, Ervan Yudha, Gerry Nugraha, Nela Fatmasari, H. D. Pranowo, J. Jumina, E. N. Sholikhah
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引用次数: 0

摘要

表皮生长因子受体(EGFR)被发现在癌细胞中过度表达,因为它控制着血管生成、细胞信号传导和增殖机制。因此,表皮生长因子受体被认为是初步筛选新型抗癌药物的常见靶点。无论是氧杂蒽酮还是查尔酮,都已被评估为抗癌剂,而它们的活性在很大程度上取决于所附官能团的类型和位置。因此,黄酮和查尔酮之间的分子杂交可以通过表皮生长因子受体抑制机制产生新型抗癌剂。在此,我们对一系列在正位、偏位和对位具有氢键受体或氢键供体取代基的黄酮-查尔酮衍生物作为表皮生长因子受体抑制剂进行了评估。研究人员设计了 37 种黄酮-查耳酮,并将其与表皮生长因子受体的活性位点对接。与原生配体相比,纯净的黄酮-查耳酮的结合能提高了1.215倍,结合常数降低了13.97倍。化合物 3SH 因其最强的结合能(-9.71 kcal/mol)和最低的结合常数(0.08 µM)而成为最有希望的候选配体。此外,分子动力学研究表明,表皮生长因子受体-3SH 复合物在 100 ns 模拟时间内是稳定的。硅学研究表明,黄酮-查尔酮衍生物是一种很有前途的新型抗癌剂,可通过体外和体内试验进行研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Molecular Docking and Molecular Dynamic Investigations of Xanthone-Chalcone Derivatives against Epidermal Growth Factor Receptor for Preliminary Discovery of Novel Anticancer Agent
Epidermal growth factor receptor (EGFR) is found to be overexpressed in cancer cells as it controls angiogenesis, cell signaling, and proliferation mechanisms. Therefore, EGFR has been known as a common target for the initial screening of new anticancer agents. Either xanthone or chalcone has been evaluated as the anticancer agents, and their activity strongly depends on the type and position of the attached functional group. Therefore, molecular hybridization between xanthone and chalcone could yield novel anticancer agents through the EGFR inhibition mechanism. Herein, a series of xanthone-chalcone derivatives with hydrogen-bond-acceptor or hydrogen-bond-donor substituents at ortho, meta, and para positions was evaluated as the EGFR inhibitor. Thirty-seven xanthone-chalcones were designed and docked in the active site of EGFR. Compared to the native ligand, pristine xanthone-chalcone gave a 1.215× stronger binding energy and a 13.97× lower binding constant. Compound 3SH was found to be the most promising candidate due to its strongest binding energy (−9.71 kcal/mol) and the lowest binding constant (0.08 µM). Furthermore, molecular dynamic studies demonstrated that complex EGFR-3SH was stable for 100 ns simulation. These in silico investigations show that the xanthone-chalcone derivative is a promising novel anticancer agent to be examined through in vitro and in vivo assays.
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来源期刊
Indonesian Journal of Chemistry
Indonesian Journal of Chemistry CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
2.30
自引率
11.10%
发文量
106
审稿时长
15 weeks
期刊介绍: Indonesian Journal of Chemistry is a peer-reviewed, open access journal that publishes original research articles, review articles, as well as short communication in all areas of chemistry, including educational chemistry, applied chemistry, and chemical engineering.
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