Synthesis and Cytotoxic Activity of Novel Indole Derivatives and Their in silico Screening on Spike Glycoprotein of SARS-CoV-2.

Kaliappillai Vijayakumar,Mohd Shahbaaz,Ponnusamy Packialakshmi,Akbar Idhayadhulla,Magda H Abdellattif,Radhakrishnan Surendrakumar,Perumal Gobinath

doi:10.3389/fmolb.2021.637989

Abstract

This work investigated the interaction of indole with SARS-CoV-2. Indole is widely used as a medical material owing to its astounding biological activities. Indole and its derivatives belong to a significant category of heterocyclic compounds that have been used as a crucial component for several syntheses of medicine. A straightforward one-pot three-component synthesis of indole, coupled with Mannich base derivatives 1a–1j, was synthesized without a catalyst. The products were confirmed by IR, 1H-NMR, 13C-NMR, mass spectra, and elemental analysis. The indole derivatives were tested for cytotoxic activity, using three cancer cell lines and normal cell lines of Human embryonic kidney cell (HEK293), liver cell (LO2), and lung cell (MRC5) by MTT assay using doxorubicin as the standard drug. The result of cytotoxicity indole compound 1c (HepG2, LC50−0.9 μm, MCF−7, LC50−0.55 μm, HeLa, LC50−0.50 μm) was found to have high activity compared with other compounds used for the same purpose. The synthesized derivatives have revealed their safety by exhibiting significantly less cytotoxicity against the normal cell line (HEK-293), (LO2), and (MRC5) with IC50 > 100 μg/ml. Besides, we report an in silico study with spike glycoprotein (SARS-CoV-2-S). The selective molecules of compound 1c exhibited the highest docking score −2.808 (kcal/mol) compared to other compounds. This research work was successful in synthesizing a few compounds with potential as anticancer agents. Furthermore, we have tried to emphasize the anticipated role of indole scaffolds in designing and discovering the much-awaited anti-SARS CoV-2 therapy by exploring the research articles depicting indole moieties as targeting SARS CoV-2 coronavirus.

Highlights

Coronavirus has proved to be the most deadly of the 21st-century epidemics by being responsible for emergent communicable disorders
All the synthesized compounds were separated by column chromatography
We have reported a facile, high-yielding, one-pot procedure for the synthesis of (1a–1j) via Mannich reaction using various kinds of protected aldehydes which was successfully employed and gave very high yields

Summary

Introduction

Coronavirus has proved to be the most deadly of the 21st-century epidemics by being responsible for emergent communicable disorders. It first manifested its presence through the onset of dangerous pneumonia, started by the (SARS-CoV) infestation in 2003 (Rahman et al, 2020). The SARS-CoV-2 has been the cause of greater than 1.27 million deaths as of November 11, 2020 (Lu et al, 2020; Wu et al, 2020; Zhou et al, 2020). The acronym for coronavirus, namely, SARSCoV-2, was assigned by the World Health Organization (WHO) on February 11, 2020 (Gorbalenya et al, 2020). SARS-CoV-2 has become a global health crisis involving around 212 countries (World Health Organization, 2020).

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