Design, Synthesis, and In Silico Studies of Novel N-(2-Aminophenyl)-2,3- Diphenylquinoxaline-6-Sulfonamide Derivatives Targeting Receptor- Binding Domain (RBD) of SARS-CoV-2 Spike Glycoprotein and their Evaluation as Antimicrobial and Antimalarial Agents

Abstract

Background: Pneumonia induced by a novel coronavirus (SARS-CoV-2) was named coronavirus disease 2019 (COVID-19). The Receptor-binding domain (RBD) of SARS-CoV-2 spike glycoprotein causes invasion of the virus into the host cell by attaching with human angiotensinconverting enzyme-2 (hACE-2), which leads to further infection. Objectives: The novel N-(2-aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives were designed and synthesized to inhibit the RBD of SARS-CoV-2 spike glycoprotein by applying molecular docking tools. Methods: The synthesized products were characterized by Infrared Spectroscopy (IR) and 1H Nuclear Magnetic Resonance (NMR). Results: All the derivatives were found to have a very good binding affinity between -9 to -10.1 kcal/mol, better than the drugs which are under investigation for the treatment of SARS-CoV-2 infection. Compound F1 formed 4 hydrogen bonds whereas, F4 and F10 formed two hydrogen bonds each with RBD of SARS-CoV-2 spike glycoprotein. All the derivatives were subjected to antimicrobial, antifungal, and antimalarial susceptibility. Conclusion: From the above-obtained results, we have concluded that novel N-(2-aminophenyl)-2,3- diphenylquinoxaline-6-sulfonamide derivatives have excellent potential to inhibit the receptorbinding domain (RBD) of SARS-CoV-2 spike glycoprotein, which is now an attentive target in designing SARS-CoV-2 inhibitors. This scaffold can hold an effective interest in the development of inhibitors for SARS-CoV-2 in the future if drug repurposing fails to serve the purpose.