Synthesis of Antibacterial Disulfide Derivatives and its Computational Molecular Docking Against Penicillin Binding Protein

Abstract

The present studies were designed to synthesize the three disulfide derivatives bearing S-S bond formation, their characterization and explore the antibacterial activity using in silico analysis. They were synthesized by the condensation reaction of 2-(2-(2-aminophenyl) disulfanyl) benzeneamine with 3-bromo-2-hydroxy-5-nitrobenzaldehyde; 5-bromo-2-hydroxybenzaldehyde and 3, 5-dichloro-2-hydroxy-benzaldehyde, respectively. The crystal structure of the compound has been crystallized in the Orthorhombic system of the space group Pbca with eight molecules in the unit cell. The compounds were elucidated by various spectroscopic methods. The molecular docking study was also performed against penicillin binding protein 4 (PBP4) active site pocket and E. coli DNA Gyrase B ATPase domain to evaluate the possible mechanism of antibacterial property of synthesized disulfide derivatives. Results revealed that these disulfide derivatives possess higher binding affinity for active site of PBP4 and Gyrase B ATPase domain. The present study demonstrated that indigenously synthesized disulfide compounds have potential to inhibit the PBP4 and Gyrase B ATPase domain and can be developed as antibacterial lead compounds. Furthermore, the LC-BLYP study provided the optimized geometry, vibrational frequency analysis and the HOMO-LUMO gap while TD-LCBLYP calculations gave the simulated UV-Visible spectra of disulfide derivatives.

GRAPHICAL ABSTRACT

Keywords:

• S-S bond formation
• Antibacterial activity
• Gyrase B inhibitor
• Penicillin binding protein
• DFT calculations