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

Al-Janabi, Ahmed S.M.; Elzupir, Amin O.; Yousef, Tarek A.

New Schiff bases {N'-(phenyl(pyridin-2-yl)methylene) isonicotinohydrazide (L(1)H), N(1)-(naphthalen-1-yl)-N(2)-(phenyl(pyridin-2-yl) methylidene) ethane-1,2-diamine (L(2)H), N-(6-chlorobenzo[d]thiazol-2-yl)-1-phenyl-1-(pyridin-2-yl) methanimine (L(3)H)}were synthesized by reaction of 2-benzoylpyridine with different amines (2-amino-6-chlorobenzothiazole, isonicotinohydrazide and N(1)-(naphthalen-1-yl)ethane-1,2-diamine) and characterized by (1)H-NMR, (13)C-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 L(3)H 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 L(3)H has the highest dipole moment and electrophilicity index. Interestingly, L(2)H 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.