Synthesis, DFT and In Silico Anti-COVID Evaluation of Novel Tetrazole Analogues

Abstract

A new series of 3-aryl/heteroaryl-2-(1H-tetrazol-5-yl) acrylamides have been synthesized through catalyst-free, one-pot cascade reactions, utilizing click chemistry approach and evaluated for their anti-COVID activities against two proteins in silico. The structural properties of the synthesized molecules were evaluated based on DFT calculations. Total energy of the synthesized tetrazole compounds were obtained through computational analysis which indicate the high stability of the synthesized compounds. The Frontier Molecular Orbitals (FMO) and associated energies and molecular electrostatic potential (MEP) surfaces were generated for the compounds. Spectral analysis by DFT gave additional evidence to the structural properties of the synthesized molecules. All tetrazole analogues come under good ADMET data as they followed the standard value for ADMET parameters. Docking studies offered evidence of the molecules displaying excellent biological properties as an anti-Covid drug. Compound 4 g exhibited excellent anti-COVID-19 properties with four hydrogen binding interactions with amino acids GLN 2.486 Å, GLN 2.436 Å, THR 2.186 Å and HSD 2.468 Å with good full-fitness score (–1189.12) and DeltaG (–7.19). Similarly, compound 4d shown potent activity against anti-COVID-19 mutant protein (PDB: 3K7H) with three hydrogen binding interactions, i.e., SER 2.274 Å, GLU 1.758 Å and GLU 1.853 Å with full-fitness score of –786.60) and DeltaG (–6.85). The result of these studies revealed that the compounds have the potential to become lead molecules in the drug discovery process.

Graphical Abstract

Keywords:

• Tetrazole
• one-pot synthesis
• click chemistry
• DFT
• ADMET
• anti-COVID

Disclosure statement

No potential conflict of interest was reported by the authors.