QSAR study of tetrahydropteridin derivatives as polo-like kinase 1(PLK1) Inhibitors with molecular docking and dynamics study.

IF 2.3 3区环境科学与生态学 Q3 CHEMISTRY, MULTIDISCIPLINARY

SAR and QSAR in Environmental Research Pub Date : 2023-02-01 Epub Date: 2023-02-06 DOI:10.1080/1062936X.2023.2167860

Garima, S Sharma, J Sindhu, P Kumar

{"title":"QSAR study of tetrahydropteridin derivatives as polo-like kinase 1(PLK1) Inhibitors with molecular docking and dynamics study.","authors":"Garima, S Sharma, J Sindhu, P Kumar","doi":"10.1080/1062936X.2023.2167860","DOIUrl":null,"url":null,"abstract":"PLK1 is the key target for dealing with different cancer because it plays an important role in cell proliferation. According to the regulation of OECD, a QSAR model was developed from a dataset of 68 tetrahydropteridin derivatives. Three descriptors (maxHaaCH, ATSC7i, AATS7m) were considered for the development of the QSAR model. The reliability and predictability of the developed QSAR model were evaluated by various statistical parameters (r2 = 0.8213, r2ext = 0.8771 and CCCext = 0.9364). The maxHaaCH descriptor is positively correlated to pIC50 whereas, the ATSC7i and AATS7m are negatively correlated with pIC50. The QSAR model explains all the structural features and shows a good correlation with the activity. Based on molecular modelling techniques, five compounds (D1-D5) were designed. Molecular docking and dynamics studies of the most active compound were performed with PDB ID: 2RKU. The results of the present investigation may be employed to identify and develop effective inhibitors for the treatment of PLK1-related pathophysiological disorders.","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":"34 2","pages":"91-116"},"PeriodicalIF":2.3000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"SAR and QSAR in Environmental Research","FirstCategoryId":"93","ListUrlMain":"https://doi.org/10.1080/1062936X.2023.2167860","RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/2/6 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 2

Abstract

PLK1 is the key target for dealing with different cancer because it plays an important role in cell proliferation. According to the regulation of OECD, a QSAR model was developed from a dataset of 68 tetrahydropteridin derivatives. Three descriptors (maxHaaCH, ATSC7i, AATS7m) were considered for the development of the QSAR model. The reliability and predictability of the developed QSAR model were evaluated by various statistical parameters (r² = 0.8213, r²_ext = 0.8771 and CCC_ext = 0.9364). The maxHaaCH descriptor is positively correlated to pIC₅₀ whereas, the ATSC7i and AATS7m are negatively correlated with pIC₅₀. The QSAR model explains all the structural features and shows a good correlation with the activity. Based on molecular modelling techniques, five compounds (D1-D5) were designed. Molecular docking and dynamics studies of the most active compound were performed with PDB ID: 2RKU. The results of the present investigation may be employed to identify and develop effective inhibitors for the treatment of PLK1-related pathophysiological disorders.

查看原文本刊更多论文

四氢蝶啶衍生物作为多聚样激酶 1（PLK1）抑制剂的 QSAR 研究以及分子对接和动力学研究

PLK1 在细胞增殖过程中发挥着重要作用，因此是治疗各种癌症的关键靶点。根据经济合作与发展组织（OECD）的规定，我们从 68 种四氢蝶啶衍生物的数据集中建立了一个 QSAR 模型。建立 QSAR 模型时考虑了三个描述因子（maxHaaCH、ATSC7i、AATS7m）。通过各种统计参数（r2 = 0.8213、r2ext = 0.8771 和 CCCext = 0.9364）评估了所建立 QSAR 模型的可靠性和可预测性。maxHaaCH 描述因子与 pIC50 呈正相关，而 ATSC7i 和 AATS7m 与 pIC50 呈负相关。QSAR 模型解释了所有的结构特征，并显示出与活性的良好相关性。根据分子建模技术，设计了五个化合物（D1-D5）。对最具活性的化合物进行了分子对接和动力学研究，PDB ID：2RKU。本研究的结果可用于鉴定和开发治疗 PLK1 相关病理生理紊乱的有效抑制剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

SAR and QSAR in Environmental Research 环境科学-毒理学

CiteScore

5.20

自引率

20.00%

发文量

审稿时长

>24 weeks

期刊介绍： SAR and QSAR in Environmental Research is an international journal welcoming papers on the fundamental and practical aspects of the structure-activity and structure-property relationships in the fields of environmental science, agrochemistry, toxicology, pharmacology and applied chemistry. A unique aspect of the journal is the focus on emerging techniques for the building of SAR and QSAR models in these widely varying fields. The scope of the journal includes, but is not limited to, the topics of topological and physicochemical descriptors, mathematical, statistical and graphical methods for data analysis, computer methods and programs, original applications and comparative studies. In addition to primary scientific papers, the journal contains reviews of books and software and news of conferences. Special issues on topics of current and widespread interest to the SAR and QSAR community will be published from time to time.