ADME Study, Molecular Docking, Elucidating the Selectivities and the Mechanism of [4 + 2] Cycloaddition Reaction Between (E)-N ((dimethylamino)methylene)benzothioamide and (S)-3-acryloyl-4-phenyloxazolidin-2-one.

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Biotechnology Pub Date : 2025-03-01 Epub Date: 2024-03-08 DOI:10.1007/s12033-024-01105-w

Mhamed Atif, Ali Barhoumi, Asad Syed, Ali H Bahkali, Mohammed Chafi, Abdessamad Tounsi, Abdellah Zeroual, Bilal Ahamad Paray, Shifa Wang, Mohammed El Idrissi

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Abstract

The molecular electron density theory (MEDT) was employed to examine the [4 + 2] cycloaddition reaction between (E)-N-((dimethylamino)methylene)benzothioamide (1) and (S)-3-acryloyl-4-phenyloxazolidin-2-one (2) at the B3LYP/6-311++G(d,p) design level. Parr functions and energy studies clearly show that this reaction is regio- and stereoselective, in perfect agreement with experimental results. By evaluating the chemical mechanism in terms of bond evolution theory (BET) and electron localization function (ELF), which divulges a variety of variations in the electron density along the reaction path, a single-step mechanism with highly asynchronous transition states structures was revealed. Additionally, we conducted a docking study on compounds P1, P2, P3, and P4 in the SARS-CoV-2 main protease (6LU7) in comparison to Nirmatrelvir. Our findings provide confirmation that product P4 may serve as a potent antiviral drug.

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ADME 研究、分子对接、阐明 (E)-N ((dimethylamino)methylene)benzothioamide 和 (S)-3-acryloyl-4-phenyloxazolidin-2-one [4 + 2] Cycloaddition 反应的选择性和机理。

在 B3LYP/6-311++G(d,p) 设计水平上，采用分子电子密度理论 (MEDT) 研究了 (E)-N-((dimethylamino)methylene)benzothioamide (1) 和 (S)-3-acryloyl-4-phenyloxazolidin-2-one (2) 之间的 [4 + 2] 环加成反应。帕尔函数和能量研究清楚地表明，该反应具有区域和立体选择性，与实验结果完全一致。化学键演化理论（BET）和电子定位功能（ELF）揭示了电子密度在反应路径上的各种变化，通过对化学机制的评估，我们发现了一种具有高度异步过渡态结构的单步机制。此外，我们还进行了化合物 P1、P2、P3 和 P4 与 SARS-CoV-2 主要蛋白酶 (6LU7) 的对接研究，并与 Nirmatrelvir 进行了对比。我们的研究结果证实，产品 P4 可作为一种有效的抗病毒药物。

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来源期刊

Molecular Biotechnology 医学-生化与分子生物学

CiteScore

4.10

自引率

3.80%

发文量

165

审稿时长

6 months

期刊介绍： Molecular Biotechnology publishes original research papers on the application of molecular biology to both basic and applied research in the field of biotechnology. Particular areas of interest include the following: stability and expression of cloned gene products, cell transformation, gene cloning systems and the production of recombinant proteins, protein purification and analysis, transgenic species, developmental biology, mutation analysis, the applications of DNA fingerprinting, RNA interference, and PCR technology, microarray technology, proteomics, mass spectrometry, bioinformatics, plant molecular biology, microbial genetics, gene probes and the diagnosis of disease, pharmaceutical and health care products, therapeutic agents, vaccines, gene targeting, gene therapy, stem cell technology and tissue engineering, antisense technology, protein engineering and enzyme technology, monoclonal antibodies, glycobiology and glycomics, and agricultural biotechnology.