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

doi:10.1007/s12033-024-01105-w

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

Mol Biotechnol. 2024 Mar 8. doi: 10.1007/s12033-024-01105-w. Online ahead of print.

Authors

Affiliations

¹ Laboratoire de Génie Environnemental, Ecologique et Agro-Industriel, Faculty of Science and Techniques of Beni Mellal, Sultan Moulay Slimane University, Beni Mellal, Morocco.
² Molecular Modelling and Spectroscopy Research Team, Faculty of Science, Chouaïb Doukkali University, P.O. Box 20, 24000, El Jadida, Morocco.
³ Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, 11451, Riyadh, Saudi Arabia.
⁴ LIPE, Higher School of Technology, Hassan II University of Casablanca, B.P 8012, Oasis, Morocco.
⁵ Molecular Modelling and Spectroscopy Research Team, Faculty of Science, Chouaïb Doukkali University, P.O. Box 20, 24000, El Jadida, Morocco. zeroualabdellah2@gmail.com.
⁶ Department of Zoology, College of Science, King Saud University, PO Box 2455, 11451, Riyadh, Saudi Arabia.
⁷ School of Electronic and Information Engineering, Chongqing Three Gorges University, Wanzhou, Chongqing, 404000, China.
⁸ Team of Chemical Processes and Applied Materials, Faculty Polydisciplinary, Sultan Moulay Slimane University, Beni-Mellal, Morocco. m.elidrissi2018@gmail.com.

PMID: 38456961
DOI: 10.1007/s12033-024-01105-w

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.

Keywords: BET; ELF; MEDT; [4 + 2] cycloaddition reaction.