# Synthesis and in silico inhibitory action studies of azo-anchored imidazo[4,5-b]indole scaffolds against the COVID-19 main protease (Mpro)

## TL;DR

This paper introduces new azo-anchored imidazo compounds that show strong potential as safe and effective inhibitors of the SARS-CoV-2 main protease.

## Contribution

The study presents a novel synthesis method and demonstrates superior in silico inhibitory activity against SARS-CoV-2 Mpro compared to existing drugs.

## Key findings

- Azo-anchored imidazo[4,5-b]indole compounds were synthesized and confirmed using spectroscopic methods.
- Molecular docking showed these compounds inhibit SARS-CoV-2 Mpro more effectively than standard drugs like Remdesivir and Paxlovid.
- The compounds exhibited minimal cytotoxicity in HEK-293 cells and favorable pharmacokinetic properties.

## Abstract

The present work elicits a novel approach to combating COVID-19 by synthesizing a series of azo-anchored 3,4-dihydroimidazo[4,5-b]indole derivatives. The envisaged methodology involves the l-proline-catalyzed condensation of para-amino-functionalized azo benzene, indoline-2,3-dione, and ammonium acetate precursors with pertinent aryl aldehyde derivatives under ultrasonic conditions. The structures of synthesized compounds were corroborated through FT-IR, 1H NMR, 13C NMR, and mass analysis data. Molecular docking studies assessed the inhibitory potential of these compounds against the main protease (Mpro) of SARS-CoV-2. Remarkably, in silico investigations revealed significant inhibitory action surpassing standard drugs such as Remdesivir, Paxlovid, Molnupiravir, Chloroquine, Hydroxychloroquine (HCQ), and (N3), an irreversible Michael acceptor inhibitor. Furthermore, the highly active compound was also screened for cytotoxicity activity against HEK-293 cells and exhibited minimal toxicity across a range of concentrations, affirming its favorable safety profile and potential suitability. The pharmacokinetic properties (ADME) of the synthesized compounds have also been deliberated. This study paves the way for in vitro and in vivo testing of these scaffolds in the ongoing battle against SARS-CoV-2.