In silico evaluation of binding interaction and ADME study of new 1,3-diazetidin-2-one derivatives with high antiproliferative activity.

IF 1.4 Q3 Pharmacology, Toxicology and Pharmaceutics Journal of Advanced Pharmaceutical Technology & Research Pub Date : 2023-07-01 Epub Date: 2023-07-28 DOI:10.4103/JAPTR.JAPTR_116_23
Farah Haidar Abdulredha, Monther Faisal Mahdi, Ayad Kareem Khan
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Abstract

A series of eight novels' 1,3-diazetidin-2-ones have been proposed to assess their potential activities. They are intended to examine antiproliferative effects through inhibition of epidermal growth factor receptor (EGFR) expression. These eight compounds strongly interact with the EGFR protein, responsible for the activity. As part of a present study, these compounds were docked to the crystal structure of the EGFR (Protein Data Bank code: 1 M17) to determine their binding affinity at the active site. Based on computer predictions, two compounds were demonstrated high scores of 80.80 and 85.89. After analyzing ADME properties, these compounds were found to have significant potential for binding. Consequently, the abilities of gefitinib, erlotinib, imatinib, and sorafenib were selected for comparison as controls. Computational methods were performed to predict the critical disposition of eight novels' 1,3-diazetidin-2-one derivatives to the EGFR. Moreover, a docking technique employing the Genetic Optimization for Ligand Docking program was conducted. Compounds 2 and 7 demonstrate a high docking peace-wise scoring function (PLP) fitness of 85.89 and 80.80, respectively. They fulfilled the Lipinski's rule, topological descriptors, and fingerprints of drug-like molecular structure keys. These compounds can be used as lead compounds to develop novel antiproliferative agents. The outcome of applying this study is novel series of 1,3-diazetidin-2-one compounds as new analogs were designed and evaluated for their antiproliferative activity with a higher potency profile and binding affinity within the active sites of EGFR.

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具有高抗增殖活性的新型1,3-二氮杂环丁烷-2-酮衍生物的结合相互作用的计算机评价和ADME研究。
已经提出了八个系列的小说的1,3-二氮杂环丁烷-2-酮来评估它们的潜在活性。它们旨在通过抑制表皮生长因子受体(EGFR)的表达来检测抗增殖作用。这八种化合物与EGFR蛋白强烈相互作用,负责活性。作为本研究的一部分,将这些化合物与EGFR(蛋白质数据库代码:1M17)的晶体结构对接,以确定它们在活性位点的结合亲和力。根据计算机预测,两种化合物的得分分别为80.80和85.89。在分析ADME性质后,发现这些化合物具有显著的结合潜力。因此,选择吉非替尼、埃洛替尼、伊马替尼和索拉非尼的能力作为对照进行比较。采用计算方法预测了8种新的1,3-二氮杂环丁烷-2-酮衍生物对EGFR的临界配置。此外,还采用了配体对接程序的遗传优化进行了对接技术。化合物2和7分别表现出85.89和80.80的高对接和平评分函数(PLP)适应度。它们满足了利平斯基规则、拓扑描述符和类药物分子结构键的指纹。这些化合物可以作为先导化合物来开发新的抗增殖剂。应用这项研究的结果是设计和评估了一系列新的1,3-二氮杂环丁烷-2-酮化合物作为新的类似物,其抗增殖活性具有更高的效力和在EGFR活性位点内的结合亲和力。
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来源期刊
CiteScore
2.00
自引率
7.10%
发文量
44
审稿时长
20 weeks
期刊介绍: Journal of Advanced Pharmaceutical Technology & Research (JAPTR) is an Official Publication of Society of Pharmaceutical Education & Research™. It is an international journal published Quarterly. Journal of Advanced Pharmaceutical Technology & Research (JAPTR) is available in online and print version. It is a peer reviewed journal aiming to communicate high quality original research work, reviews, short communications, case report, Ethics Forum, Education Forum and Letter to editor that contribute significantly to further the scientific knowledge related to the field of Pharmacy i.e. Pharmaceutics, Pharmacology, Pharmacognosy, Pharmaceutical Chemistry. Articles with timely interest and newer research concepts will be given more preference.
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