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

Title: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

Volume: 18 Issue: 9

Author(s): Falak A. Siddiqui, Sharuk L. Khan*, Rajendra P. Marathe and Nitin V. Nema

Affiliation:

• Department of Pharmaceutical Chemistry, MUP’s College of Pharmacy (B Pharm), Degaon, Risod, Washim, Maharashtra,India

Keywords: Design, synthesis, COVID-19, quinoxaline-sulphonamide, antifungal, PyRx virtual screening tool, molecular docking.

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.

Objective: 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.

Cite this article as:

Siddiqui A. Falak, Khan L. Sharuk *, Marathe P. Rajendra and Nema V. Nitin , 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, Letters in Drug Design & Discovery 2021; 18 (9) . https://dx.doi.org/10.2174/1570180818666210427095203