Background:
The diazenyl compounds (-N=N- linkage) have been reported to have antimicrobial
activity. In modern drug discovery, the drug-receptor interactions are generally explored by the
molecular docking studies.
Materials and Methods:
Three categories of diazenyl scaffolds were screened for the docking studies
to explore the binding mechanism of interaction with various microbial targets. The diazenyl Schiff
bases (SBN-20, SBN-21, SBN-25, SBN-33, SBN-39, SBN-40 and SBN-42), naphthol pharmacophore
based diazenyl Schiff bases (NS-2, NS-8, NS-12, NS-15, NS-21, and NS-23), morpholine based diazenyl
chalcones (MD-6, MD-9, MD-14, MD-16, MD-20, and MD-21) were docked against various
bacterial and fungal proteins in comparison with different standard drugs. Further, the drug likeliness
and ADME properties of these molecules were predicted by QikProp module of the Schrodinger software.
Results:
Most of the derivatives had shown less docking scores and binding energies towards bacterial
proteins, such as dihydropteroate synthase (PDB:2VEG), glucosamine-6-phosphate synthase
(PDB:2VF5), dihydrofolate reductase (PDB:3SRW) in comparison with the standard drugs. The naphthol
based diazenyl Schiff bases NS-21 and NS-23 were predicted to act on the cytochrome P450 sterol
14-alpha-demethylase (CYP51) (PDB:5FSA) involved in sterol biosynthesis, an essential target for
antifungal drugs. The derivative MD-6, NS-2, NS-21, and NS-23 had shown high docking scores
against bacterial DNA topoisomerase (PDB:3TTZ) in comparison with the standard drug ciprofloxacin.
Further, most of the synthesized derivatives had shown drug like characters.
Conclusion:
Hence, these compounds can be developed as novel antibacterial agents as potent DNA
topoisomerase inhibitors and antifungal agents as CYP51 inhibitors.
Chemical-informatics approach to COVID-19 drug discovery: Monte Carlo based QSAR, virtual screening and molecular docking study of some in-house molecules as papain-like protease (PLpro) inhibitors
