Synthesis, anti-bacterial evaluation, DFT study and molecular docking as a potential 3-chymotrypsin-like protease (3CLpro) of SARS-CoV-2 inhibitors of a novel Schiff bases

•Synthesis new Schiff bases and characterized by IR, NMR and elemental analysis.•In vitro antibacterial activity were investigated.•Calculations of the density functional theory.•The synthetic compounds have also been docked with 3-chymotrypsin-like protease (3CLpro). New Schiff bases {N'-(phenyl(pyridin-2-yl)methylene) isonicotinohydrazide (L1H), N1-(naphthalen-1-yl)-N2-(phenyl(pyridin-2-yl) methylidene) ethane-1,2-diamine (L2H), N-(6-chlorobenzo[d]thiazol-2-yl)-1-phenyl-1-(pyridin-2-yl) methanimine (L3H)}were synthesized by reaction of 2-benzoylpyridine with different amines (2-amino-6-chlorobenzothiazole, isonicotinohydrazide and N1-(naphthalen-1-yl)ethane-1,2-diamine) and characterized by 1H-NMR, 13C-NMR, IR mass spectroscopy and elemental analysis. The compounds were assayed by the disc diffusion method for anti-bacterial against five pathogenic bacteria species (Staphylococcus aureus, Micrococcus luteus, Staphylococcus pyogenes, Bacillus subtilis, and E. coli). All prepared Schiff bases showed good activity compared to positive control (streptomycin), Moreover the L3H showed the highest activity against S. aureus, and M. luteus than the other compounds and streptomycin. In additional molecular docking studies with 3-chymotrypsin-like protease (3CLpro), the essential enzyme for SARS-CoV-2 proliferation. The rest of compounds have shown promising results as 3CLpro inhibitors interacting with the active sites of the enzymes. Finally, DFT 's estimated electrostatic molecular potential results were used to illustrate the molecular docking findings. The DFT calculations showed that L3H has the highest dipole moment and electrophilicity index. Interestingly, L2H of the largest energy gap ∆E = 2.49 eV, there are several hydrophilic interactions that could facilitate the binding with the receptors. All of these parameters could be shared to significantly affect the protein sites of binding affinity with different extent.