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.

[1]  B. El Bali,et al.  Synthesis, α-Glucosidase Inhibition, Anticancer, DFT and Molecular Docking Investigations of Pyrazole Hydrazone Derivatives , 2022, Polycyclic Aromatic Compounds.

[2]  H. Louis,et al.  Antimicrobial activities of 1-phenyl-3-methyl-4-trichloroacetyl-pyrazolone: Experimental, DFT studies, and molecular docking investigation , 2022, Journal of the Indian Chemical Society.

[3]  N. Dharani,et al.  Multi-target potential of Indian phytochemicals against SARS-CoV-2: A docking, molecular dynamics and MM-GBSA approach extended to Omicron B.1.1.529. , 2022, Journal of Infection and Public Health.

[4]  E. Şahin,et al.  Experimental and computational studies of 1,5-diphenyl-pyrazole-3-carboxamide compounds as potential Cannabinoid receptor type 1 , 2022, Journal of Molecular Structure.

[5]  S. Radi,et al.  Synthesis and investigations of reactive properties, photophysical properties and biological activities of a pyrazole-triazole hybrid molecule. , 2022, Journal of Molecular Structure.

[6]  Mubashir Hassan,et al.  Elastase inhibitory activity of quinoline Analogues: Synthesis, kinetic mechanism, cytotoxicity, chemoinformatics and molecular docking studies. , 2022, Bioorganic & medicinal chemistry.

[7]  Weiying Zhang,et al.  Challenges and countermeasures brought by Omicron Variant , 2022, Journal of Microbiology, Immunology and Infection.

[8]  Mehdi Messaad,et al.  Synthesis, bioassay and molecular docking of novel pyrazole and pyrazolone derivatives as acetylcholinesterase inhibitors , 2022, Journal of Molecular Structure.

[9]  A. Abbasi,et al.  Synthesis and crystal structures of new mixed-ligand schiff base complexes containing N-donor heterocyclic co-ligands: Molecular docking and pharmacophore modeling studies on the main proteases of SARS-CoV-2 virus (COVID-19 disease) , 2022, Polyhedron.

[10]  Kaushal P. Patel,et al.  Microwave-assisted synthesis of pyrano[2,3-c]-pyrazole derivatives and their anti-microbial, anti-malarial, anti-tubercular, and anti-cancer activities , 2022, Journal of Molecular Structure.

[11]  Hasti Iranmanesh,et al.  Experimental and computational studies on copper(II) Schiff base complex derived from 4-acetyl-3-methyl-1-phenyl-2-pyrazolin-5-one , 2022, Journal of Molecular Structure.

[12]  R. Abonía,et al.  Synthesis, Structural Characterization, and In Vitro and In Silico Antifungal Evaluation of Azo-Azomethine Pyrazoles (PhN2(PhOH)CHN(C3N2(CH3)3)PhR, R = H or NO2) , 2021, Molecules.

[13]  W. Jang,et al.  Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay , 2021, Proceedings of the National Academy of Sciences.

[14]  M. Peana,et al.  Chloroquine and hydroxychloroquine in the treatment of COVID-19: the never-ending story , 2021, Applied Microbiology and Biotechnology.

[15]  Khaled N. M. Elsayed,et al.  Combination and tricombination therapy to destabilize the structural integrity of COVID-19 by some bioactive compounds with antiviral drugs: insights from molecular docking study , 2021, Structural Chemistry.

[16]  M. Ferbinteanu,et al.  Synthesis, X-ray structure, vibrational spectroscopy, DFT, biological evaluation and molecular docking studies of (E)-N’-(4-(dimethylamino)benzylidene)-5-methyl-1H-pyrazole-3-carbohydrazide , 2020 .

[17]  P. Singour,et al.  Finding potent inhibitors for COVID-19 main protease (Mpro): an in silico approach using SARS-CoV-3CL protease inhibitors for combating CORONA , 2020, Journal of biomolecular structure & dynamics.

[18]  W. Ye,et al.  Potential of coronavirus 3C-like protease inhibitors for the development of new anti-SARS-CoV-2 drugs: Insights from structures of protease and inhibitors , 2020, International Journal of Antimicrobial Agents.

[19]  Shakiba Darvish Alipour Astaneh,et al.  Copper complexes of pyrazolone-based Schiff base ligands: Synthesis, crystal structures and antibacterial properties , 2020 .

[20]  C. Pettinari,et al.  Coordination chemistry of pyrazolone-based ligands and applications of their metal complexes , 2019 .

[21]  M. Lutz.  Metamizole (Dipyrone) and the Liver: A Review of the Literature , 2019, Journal of clinical pharmacology.

[22]  Ki‐Hyun Kim,et al.  A review of the applications of Schiff bases as optical chemical sensors , 2019, TrAC Trends in Analytical Chemistry.

[23]  Rehab G El-sharkawy,et al.  Multi-walled carbon nanotubes decorated with Cu(II) triazole Schiff base complex for adsorptive removal of synthetic dyes , 2019, Journal of Molecular Liquids.

[24]  H. El‐Ghamry,et al.  Synthesis, spectroscopic, thermal and molecular modeling studies of Zn2+, Cd2+ and UO22+ complexes of Schiff bases containing triazole moiety. Antimicrobial, anticancer, antioxidant and DNA binding studies. , 2018, Materials science & engineering. C, Materials for biological applications.

[25]  H. El‐Ghamry,et al.  Synthesis, spectroscopic and DNA binding ability of CoII, NiII, CuII and ZnII complexes of Schiff base ligand (E)-1-(((1H-benzo[d]imidazol-2-yl)methylimino)methyl)naphthalen-2-ol. X-ray crystal structure determination of cobalt (II) complex. , 2017, Materials science & engineering. C, Materials for biological applications.

[26]  H. El‐Ghamry,et al.  Synthesis, Characterization, and Catalytic Activity of New Cu(II) Complexes of Schiff Base: Effective Catalysts for Decolorization of Acid Red 37 Dye Solution , 2015 .

[27]  A. Moustafa,et al.  Synthesis and Analgesic Activity of Some New Pyrazoles and Triazoles Bearing a 6,8-Dibromo-2-methylquinazoline Moiety , 2011, Molecules.

[28]  C. Pettinari,et al.  Acylpyrazolone ligands : Synthesis, structures, metal coordination chemistry and applications , 2005 .

[29]  Jamshid Rakhtshah.  A comprehensive review on the synthesis, characterization, and catalytic application of transition-metal Schiff-base complexes immobilized on magnetic Fe3O4 nanoparticles , 2022, Coordination Chemistry Reviews.

[30]  B. Jensen,et al.  THE SYNTHESIS OF 1-PHENYL-3-METHYL-4-ACYL-PYRAZOLONES-5 , 1959 .