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

Mhamed Atif1, Ali Barhoumi2, Asad Syed3, Ali H. Bahkali3, Mohammed Chafi4, Abdessamad Tounsi1, Abdellah Zeroual2, Bilal Ahamad Paray5, Shifa Wang6, Mohammed El Idrissi7
1Laboratoire de Génie Environnemental, Ecologique et Agro-Industriel, Faculty of Science and Techniques of Beni Mellal, Sultan Moulay Slimane University, Beni Mellal, Morocco
2Molecular Modelling and Spectroscopy Research Team, Faculty of Science, Chouaïb Doukkali University, El Jadida, Morocco
3Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
4LIPE, Higher School of Technology, Hassan II University of Casablanca, Oasis, Morocco
5Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
6School of Electronic and Information Engineering, Chongqing Three Gorges University, Chongqing, China
7Team of Chemical Processes and Applied Materials, Faculty Polydisciplinary, Sultan Moulay Slimane University, Beni-Mellal, Morocco

Tóm tắt

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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