新型氨磺酰氧基恶唑烷酮的合成、研究（密度泛函理论、药物代谢和毒性预测）及晶体结构：与严重急性呼吸综合征冠状病毒2的相互作用

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

作者信息

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

机构信息

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.

Unité de Recherche de Chimie de L'Environnement et Moléculaire Structurale, Université des Fréres Mentouri, Constantine 25000, Algeria.

出版信息

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

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.

已合成了一系列新的氨磺酰氧基恶唑烷酮（SOO）衍生物，并通过单晶X射线衍射、核磁共振、红外光谱、质谱和元素分析对其进行了表征。使用密度泛函理论（DFT）方法研究了目标化合物的化学反应性和几何特征。利用分子对接模拟研究了SOO与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）主要蛋白酶（Mpro）之间可能的结合模式及其反应性。单晶X射线衍射表明，SOO以单斜晶系P 2 1空间群结晶。SARS-CoV-2/Mpro-SOO复合物的结合能以及使用对接模拟计算的抑制常数表明，活性SOO分子具有抑制SARS-CoV-2的能力。我们研究了合成分子的吸收、分布、代谢、排泄和毒性（ADMET）预测。