A C de Faria, A P L de Mesquita, E F F da Cunha, M P Freitas
{"title":"苯并噻唑和邻苯二胺衍生物杂合体作为原卟啉原IX氧化酶抑制剂的硅晶设计。","authors":"A C de Faria, A P L de Mesquita, E F F da Cunha, M P Freitas","doi":"10.1080/1062936X.2025.2496156","DOIUrl":null,"url":null,"abstract":"<p><p>Protoporphyrinogen IX oxidase (PPO) inhibition is a critical strategy for weed control in crop production. This study employed a computational approach integrating QSAR modelling, docking studies, and molecular dynamics to investigate the inhibitory activities of benzothiazole- and phthalimide-derived compounds against PPO. The MIA-QSAR method modelled p<i>K</i>i values for 52 compounds, complemented by docking and molecular dynamics to analyse ligand-enzyme interactions and identify potential agrochemical candidates. QSAR analysis yielded predictive models with <i>r</i><sup>2</sup> = 0.77, <i>q</i><sup>2</sup> = 0.55, and <i>r</i><sup>2</sup> = 0.74. MIA plots guided the design of 12 derivatives, 5 of which showed promising p<i>K</i>i values (7.31-8.69). Docking and molecular dynamics revealed strong binding affinity and stability for these candidates. The presence of fluorine substituents and C=O and C=S bonds in tetrahydroisoindole moieties enhanced biological activity, leading to the proposition of effective PPO inhibitors. Synthetic routes for the top candidates were outlined for future development, aiming to improve agrochemical efficacy and address resistance issues in crop protection.</p>","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":" ","pages":"287-303"},"PeriodicalIF":2.3000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In silico design of benzothiazole and phthalimide-derived hybrids as protoporphyrinogen IX oxidase inhibitors.\",\"authors\":\"A C de Faria, A P L de Mesquita, E F F da Cunha, M P Freitas\",\"doi\":\"10.1080/1062936X.2025.2496156\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Protoporphyrinogen IX oxidase (PPO) inhibition is a critical strategy for weed control in crop production. This study employed a computational approach integrating QSAR modelling, docking studies, and molecular dynamics to investigate the inhibitory activities of benzothiazole- and phthalimide-derived compounds against PPO. The MIA-QSAR method modelled p<i>K</i>i values for 52 compounds, complemented by docking and molecular dynamics to analyse ligand-enzyme interactions and identify potential agrochemical candidates. QSAR analysis yielded predictive models with <i>r</i><sup>2</sup> = 0.77, <i>q</i><sup>2</sup> = 0.55, and <i>r</i><sup>2</sup> = 0.74. MIA plots guided the design of 12 derivatives, 5 of which showed promising p<i>K</i>i values (7.31-8.69). Docking and molecular dynamics revealed strong binding affinity and stability for these candidates. The presence of fluorine substituents and C=O and C=S bonds in tetrahydroisoindole moieties enhanced biological activity, leading to the proposition of effective PPO inhibitors. Synthetic routes for the top candidates were outlined for future development, aiming to improve agrochemical efficacy and address resistance issues in crop protection.</p>\",\"PeriodicalId\":21446,\"journal\":{\"name\":\"SAR and QSAR in Environmental Research\",\"volume\":\" \",\"pages\":\"287-303\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"SAR and QSAR in Environmental Research\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://doi.org/10.1080/1062936X.2025.2496156\",\"RegionNum\":3,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/6 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.2025.2496156","RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/6 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
In silico design of benzothiazole and phthalimide-derived hybrids as protoporphyrinogen IX oxidase inhibitors.
Protoporphyrinogen IX oxidase (PPO) inhibition is a critical strategy for weed control in crop production. This study employed a computational approach integrating QSAR modelling, docking studies, and molecular dynamics to investigate the inhibitory activities of benzothiazole- and phthalimide-derived compounds against PPO. The MIA-QSAR method modelled pKi values for 52 compounds, complemented by docking and molecular dynamics to analyse ligand-enzyme interactions and identify potential agrochemical candidates. QSAR analysis yielded predictive models with r2 = 0.77, q2 = 0.55, and r2 = 0.74. MIA plots guided the design of 12 derivatives, 5 of which showed promising pKi values (7.31-8.69). Docking and molecular dynamics revealed strong binding affinity and stability for these candidates. The presence of fluorine substituents and C=O and C=S bonds in tetrahydroisoindole moieties enhanced biological activity, leading to the proposition of effective PPO inhibitors. Synthetic routes for the top candidates were outlined for future development, aiming to improve agrochemical efficacy and address resistance issues in crop protection.
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.