Synthesis and Molecular Docking of New 1,2,3-triazole Carbohydrates with COVID-19 Proteins

Abstract

Aims: With this aim, we have established this paper to recommend a novel way for the preparation of carbohydrates encompassing a 1,2,3-triazole motif that were prepared using an efficient click chemistry synthesis. Background: The SARS-CoV-2 coronavirus epidemic continues to spread at a fast rate worldwide. The main protease (Mpro) is a gorgeous target for anti-COVID-19 agents. Triazoles are frequently found in many bioactive products such as coronavirus inhibitors. Objective: Click reactions are facilitated via the activation of copper nanoparticles, different substrates have been tested using this adopted procedure given in all cases, in high yields and purity. Other interesting comparative docking analyzes will be the focus of this article. Calculations of quantitative structure-activity relationships will be studied. Method: Copper nanoparticles were produced by the reaction of cupric acetate monohydrate with oleylamine and oleic acid. To a solution 5-(azidomethyl)-2,2,7,7-tetramethyltetrahydro-5H-bis([1,3]dioxolo)[4,5-b:4',5'-d]pyran 2 (200 mg, 0.72 mmol, 1 eq.) in toluene (15 mL) was added (1.5 eq.) of N-(prop-2-yn-1-yl)benzamide derivatives 1a-d, copper nanoparticles (0.57 mg, 0.036 mmol, 0.05 eq.). Result: A novel series of 1,2,3-triazole carbohydrate skeletons were modeled and efficiently synthesized. Based on the observations of virtual screening established using molecular docking performed to identify novel compounds that can be able to bind with the protein structures of COVID-19 (PDB ID: 6LU7 and 6W41), we believed that the 1,2,3-triazole carbohydrate derivatives could aid in COVID-19 drug discovery. Conclusion: The formations of targeted triazoles were confirmed by different spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, and CHN analysis). The docking scores of the newly synthesized triazole are maybe attributed to the presence of hydrogen bonds together with many interactions between the ligands and the active amino acid residue of the receptor. The comparison of the interactions of remdesivir drug and triazole in the largest pocket of 6W41 and 6LU7 is also presented.