Synthesis, in silico study (DFT, ADMET) and crystal structure of novel sulfamoyloxy-oxazolidinones: Interaction with SARS-CoV-2

Abdeslem Bouzina; Malika Berredjem; Sofiane Bouacida; Khaldoun Bachari; Christelle Marminon; Marc Le Borgne; Zouhair Bouaziz; Yousra Ouafa Bouone

doi:10.1016/j.molstruc.2022.132579

Synthesis, in silico study (DFT, ADMET) and crystal structure of novel sulfamoyloxy-oxazolidinones: Interaction with SARS-CoV-2

J Mol Struct. 2022 Jun 5:1257:132579. doi: 10.1016/j.molstruc.2022.132579. Epub 2022 Feb 5.

Authors

Abdeslem Bouzina¹, Malika Berredjem¹, Sofiane Bouacida^{2

3}, Khaldoun Bachari⁴, Christelle Marminon⁵, Marc Le Borgne⁵, Zouhair Bouaziz⁶, Yousra Ouafa Bouone¹

Affiliations

¹ Department of Chemistry, Laboratory of Applied Organic Chemistry, Synthesis of Biomolecules and Molecular Modelling Group, Sciences Faculty, Badji-Mokhtar-Annaba University, Box 12, Annaba 23000, Algeria.
² Unité de Recherche de Chimie de L'Environnement et Moléculaire Structurale, Université des Fréres Mentouri, Constantine 25000, Algeria.
³ Département des Sciences de La Matiére, Université Larbi Ben M'Hidi, Oum El Bouaghi 04000, Algeria.
⁴ Centre de Recherche Scientifique et Technique en Analyses Physico-Chimiques (CRAPC), BP384, Bou-Ismail, Tipasa RP 42004, Algeria.
⁵ Small Molecules for Biological Targets Team, Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, CNRS 5286, INSERM 1052, Université Claude Bernard Lyon 1, Univ Lyon, Lyon 69373, France.
⁶ Faculté de Pharmacie-ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453-INSERM US7, Université de Lyon, Université Lyon 1, CEDEX 8, Lyon 69373, France.

Abstract

A new series of sulfamoyloxyoxazolidinone (SOO) derivatives have been synthesized and characterized by single-crystal X-ray diffraction, NMR, IR, MS and EA. Chemical reactivity and geometrical characteristics of the target compounds were investigated using DFT method. The possible binding mode between SOO and Main protease (Mpro) of SARS-CoV-2 and their reactivity were studied using molecular docking simulation. Single crystal X-ray diffraction showed that SOO crystallizes in a monoclinic system with P 2 1 space group. The binding energy of the SARS-CoV-2/Mpro-SOO complex and the calculated inhibition constant using docking simulation showed that the active SOO molecule has the ability to inhibit SARS-CoV2. We studied the prediction of absorption, distribution, properties of metabolism, excretion and toxicity (ADMET) of the synthesized molecules.

Keywords: Crystal structure; DFT study; In silico study; Molecular docking; SARS-CoV-2; Sulfamoyloxy-oxazolidinone.