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。

IF 2.3 3区 环境科学与生态学 Q3 CHEMISTRY, MULTIDISCIPLINARY
A C de Faria, A P L de Mesquita, E F F da Cunha, M P Freitas
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引用次数: 0

摘要

抑制原卟啉原IX氧化酶(PPO)是作物生产中控制杂草的重要策略。本研究采用QSAR建模、对接研究和分子动力学相结合的计算方法,研究了苯并噻唑和邻苯二甲酰亚胺衍生化合物对PPO的抑制活性。MIA-QSAR方法模拟了52种化合物的pKi值,辅以对接和分子动力学来分析配体-酶的相互作用,并确定潜在的农用化学品候选物。QSAR分析得到的预测模型r2 = 0.77, q2 = 0.55, r2 = 0.74。MIA图指导了12个衍生物的设计,其中5个衍生物的pKi值很有希望(7.31-8.69)。对接和分子动力学表明这些候选物具有很强的结合亲和力和稳定性。氟取代基和四氢异吲哚基团中C=O和C=S键的存在增强了生物活性,从而提出了有效的PPO抑制剂。概述了未来开发的最佳候选化合物的合成路线,旨在提高农用化学品的功效并解决作物保护中的抗性问题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
CiteScore
5.20
自引率
20.00%
发文量
78
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.
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