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

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

doi:10.1016/j.molstruc.2020.129454

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

J Mol Struct. 2021 Mar 15:1228:129454. doi: 10.1016/j.molstruc.2020.129454. Epub 2020 Oct 17.

Authors

Ahmed S M Al-Janabi¹, Amin O Elzupir², Tarek A Yousef^{3

4}

Affiliations

¹ Department of Biochemistry, College of Veterinary Medicine, Tikrit University, Tikrit, Iraq.
² Imam Mohammad Ibn Saud Islamic University (IMSIU), College of Science, Deanship of Scientific Research, Riyadh, KSA.
³ Department of Chemistry, Science College, Imam Mohammad Ibn Saud Islamic University, (IMSIU), Riyadh, KSA, P.O. Box 90950, Riyadh 11623, Saudi Arabia.
⁴ Toxic and Narcotic drug, Forensic Medicine Department, Mansoura Laboratory, Medicolegal organization, Ministry of Justice, Egypt.

Abstract

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 N ¹-(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.

Keywords: COVID 19; DFT calculations; Molecular docking; Schiff bases.