{"title":"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","authors":"Garima, S Sharma, J Sindhu, P Kumar","doi":"10.1080/1062936X.2023.2167860","DOIUrl":null,"url":null,"abstract":"<p><p>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 (<i>r</i><sup>2</sup> = 0.8213, <i>r</i><sup>2</sup><sub>ext</sub> = 0.8771 and CCC<sub>ext</sub> = 0.9364). The maxHaaCH descriptor is positively correlated to pIC<sub>50</sub> whereas, the ATSC7i and AATS7m are negatively correlated with pIC<sub>50</sub>. 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.</p>","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":"{\"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\":\"<p><p>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 (<i>r</i><sup>2</sup> = 0.8213, <i>r</i><sup>2</sup><sub>ext</sub> = 0.8771 and CCC<sub>ext</sub> = 0.9364). The maxHaaCH descriptor is positively correlated to pIC<sub>50</sub> whereas, the ATSC7i and AATS7m are negatively correlated with pIC<sub>50</sub>. 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.</p>\",\"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}","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}
QSAR study of tetrahydropteridin derivatives as polo-like kinase 1(PLK1) Inhibitors with molecular docking and dynamics study.
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.
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.
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