Design, Spectroscopic, and Crystal Structural Characterization of New Pyrazolone-Based Schiff Bases: Molecular Docking Investigations against SARS-Covid-19 Main Proteases (PDB Ids: 6LU7 and 7TLL)

New pyrazolone-based Schiff bases were synthesized and characterized by various spectroscopic and analytical techniques such as 1H-NMR, FTIR, and UV − Vis spectroscopy and elemental analysis. Crystal structures of two of the Schiff-base (SB) compounds were obtained by single-crystal X-ray crystallography (SCXRC). The target Schiff bases were synthesized from the condensation of 4-acetyl-3-methyl-1-phenyl-5-pyrazolone with 1,2-diaminobenzene (SB1), 4-methyl-1,2-diaminobenzene (SB2), and 4,5-dimethy-1,2-diaminobenzene (SB3). Molecular docking modeling was used to study the interactions of these molecules with SARS-CoV-2 virus main proteases (PDB ids: 6LU7 and 7TLL). The estimated free binding energies (EFBE) for all the three SBs were better than the standard drugs favipiravir and dexamethasone. Besides, the order of EFBE was −7.68 (SB3)> −7.36 (SB1)> −7.06 kcal.mol−1 (SB2) for 6LU7 and −10.42 (SB3)> −10.05 (SB1)> −9.69 kcal.mol−1 (SB2) for 7TLL. SB3 showed the best interactions with both proteases that is discussed based on structure–function relationship.