Persuasive phytoestrogenic imidazole-based selenium N-heterocyclic carbenes: electronic, structural, and in silico anticancer potential investigations

IF 2.1 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Sadaf Mutahir, Muhammad Asim Khan, Iqra Asif, Zeeshan Mutahir, Abdulrahman A. Almehizia, Muhammad Atif Tariq
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Abstract

The cellular antioxidant defense mechanism against reactive oxygen species (ROS) depends on selenium, a vital trace element. Numerous selenium-containing compounds have recently displayed a wide range of biological characteristics that make them intriguing scaffolds in medicinal chemistry. Among the several categories of phytoestrogens, Imidazole-Based Selenium N-heterocyclic carbene Compounds (IM-SeNHC) have drawn the most scientific attention. Several IM-SeNHC compounds were chosen for this theoretical study analysis. The goal of this study was to govern the binding capacity of each of the selected IM-SeNHC that have been identified as inhibitors of the proteins responsible for cancer EGFR, hTrkA, HER2, and cMet (PDB codes: 5GTY, 6PL2, 7JXH, and 3RHK, respectively). DFT and molecular docking investigations were carried out employing in silico software for their virtual screening. Conferring to the docking study, ligand 6 formed hydrogen bonds with protein 7JXH’s active pocket, followed by ligand 8 with protein 3RHK and 5GTY, and ligand 9 with protein 6PL2. Conferring to trends in polarizability and dipole moment, the energy difference values (0.299 eV and 0.277 eV) of IM-SeNHC compounds (3 and 8) show the rise in chemical potential, reactivity, and bioactivity brought on by the most stable structural configurations. Additionally, ADME was investigated to discover the pharmacokinetic characteristics of the targeted moieties. The cardiotoxicity analysis was performed, and confidence percentages accompanying these predictions vary across the dataset, ranging from around 57 to 99.9%, indicating differing levels of certainty in the predictions. This research showed that these ligands have a promising future in cancer therapy medications.

Abstract Image

具有植物雌激素说服力的咪唑基硒 N-杂环碳烯:电子、结构和硅学抗癌潜力研究
摘要 针对活性氧(ROS)的细胞抗氧化防御机制依赖于硒这种重要的微量元素。最近,许多含硒化合物显示出了广泛的生物学特性,使它们成为药物化学中引人入胜的支架。在几类植物雌激素中,咪唑基硒 N-杂环碳化物(IM-SeNHC)最受科学界关注。本研究选择了几种 IM-SeNHC 化合物进行理论研究分析。本研究的目标是对已被确定为表皮生长因子受体、hTrkA、HER2 和 cMet 癌症蛋白(PDB 代码分别为 5GTY、6PL2、7JXH 和 3RHK)抑制剂的 IM-SeNHC 的结合能力进行检测。研究人员利用硅学软件进行了 DFT 和分子对接研究,以进行虚拟筛选。根据对接研究,配体 6 与蛋白质 7JXH 的活性口袋形成氢键,配体 8 与蛋白质 3RHK 和 5GTY 形成氢键,配体 9 与蛋白质 6PL2 形成氢键。根据极化性和偶极矩的变化趋势,IM-SeNHC 化合物(3 和 8)的能差值(0.299 eV 和 0.277 eV)显示了最稳定结构构型带来的化学势、反应性和生物活性的提高。此外,还对 ADME 进行了研究,以发现目标分子的药代动力学特征。进行了心脏毒性分析,这些预测的置信度在整个数据集中各不相同,从大约 57% 到 99.9%,表明预测的确定性水平各不相同。这项研究表明,这些配体在癌症治疗药物中大有可为。
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来源期刊
Structural Chemistry
Structural Chemistry 化学-化学综合
CiteScore
3.80
自引率
11.80%
发文量
227
审稿时长
3.7 months
期刊介绍: Structural Chemistry is an international forum for the publication of peer-reviewed original research papers that cover the condensed and gaseous states of matter and involve numerous techniques for the determination of structure and energetics, their results, and the conclusions derived from these studies. The journal overcomes the unnatural separation in the current literature among the areas of structure determination, energetics, and applications, as well as builds a bridge to other chemical disciplines. Ist comprehensive coverage encompasses broad discussion of results, observation of relationships among various properties, and the description and application of structure and energy information in all domains of chemistry. We welcome the broadest range of accounts of research in structural chemistry involving the discussion of methodologies and structures,experimental, theoretical, and computational, and their combinations. We encourage discussions of structural information collected for their chemicaland biological significance.
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