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)

Abstract

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.

Keywords:

• Covid-19
• pyrazolone-based Schiff base
• molecular docking

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Disclosure statement

The authors have no relevant financial or non-financial interests to disclose.

Authors’ contribution

All authors contributed to the study conception and design. Maryam Hasanzadeh Esfahani synthesized the compounds and characterized them. Liana Ghasemi performed the molecular docking studies and wrote the initial draft of the manuscript. Eliska Skorepova obtained the crystal structures, read and edited the manuscript. Michal Dusek was the head of the crystallography. Mahdi Behzad supervised the experiments and wrote and edited the manuscript.

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The data and material that support the findings of this study are available from the corresponding author upon reasonable request.

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The authors declare that no funds, grants, or other supports were received during the preparation of this manuscript.