Design, synthesis and molecular modeling of isatin-aminobenzoic acid hybrids as antibacterial and antibiofilm agents.

Number of factors, including newly emerging infectious diseases and an increase in multi-drug resistant microbial pathogens with particular relevance for bacteria, make the treatment of infectious diseases in hospital-based healthcare a major challenge in the medical community. 4-Aminobenzoic acid (PABA), has demonstrated a variety of biological actions particularly, antimicrobial activity. In our study we coupled this vitamin-like molecule with different isatin derivatives. We investigated the antibacterial activity of the synthesized Schiff's bases. The compounds showed high selective activity against -positive bacteria and showed weak or no activity against both -negative bacteria and fungi. Compound showed highest activity against and (MIC 0.09 mmol/L). Additionally, these substances exhibit strong anti- biofilm formation. We were able to shed insight on the binding mode of these new inhibitors using in silico docking of the compounds in the binding sites of a 3D structure of histidine kinase/Walk. The binding free energy of the compound to the catalytic domain walk, of histidine kinase enzyme of bacteria, was calculated using molecular mechanics/generalized born surface area scoring. The key residues for macromolecule-ligand binding were postulated. The optimized 3D protein-ligand binding modes shed light on the B. subtilis HK/Walk-ligand interactions that afford a means to assess binding affinity to design new HK/Walk inhibitor as antibacterial agents.