Synthesis and molecular docking simulation on the antimicrobial effects of halogenated vanillin-azo dyes and schiff base derivatives

Lead compounds containing nitrogen pharmacophores from natural resources have garnered interest among researchers due to their potential for drug development. However, the extractions of the active metabolites are usually labor-intensive and time-consuming. In this study, halogenated vanillin derivatives featuring azo dyes (N=N) ( 1a-1 h ) and Schiff base (C=N) ( 2a-2 h ) have been synthesized via diazonium coupling and nucleophilic substitution reaction, respectively. The comparative effect of N=N and C=N moieties was evaluated for antibacterial properties against Staphylococcus aureus and Escherichia coli via disc diffusion method. Incorporating C=N (8–13 mm) into the vanillin network showed excellent inhibition against S. aureus compared to N=N (7–8 mm) and the standard ampicillin (12 mm). While the halogenated vanillin featuring N=N (7–9 mm) and C=N (7–8 mm) moieties showed excellent zone of inhibitions against E. coli compared to the parent vanillin. The in-silico screening using AutoDock Vina, showed 2c-h (inhibition zone > 10 mm) with a high binding affinity against DNA gyrase enzyme with binding energy ranging from − 7.3 to − 7.9 kcal/mol, similar to re-docking of ampicillin − 7.6 kcal/mol and co-crystalize compounds BPH651 with − 7.5 kcal/mol. This research contributes a significant milestone in drug design, especially for the development of new antibacterial drugs with outstanding properties. Graphical abstract Article Highlights A synergistic effect of functional groups in vanillin-Schiff base (C=N) and vanillin-azo dyes (N=N) contributed to the hydrogen bond interaction with the biological receptors. Structure–Activity relationship of halogenated vanillin derivatives supported the inhibition activity against Staphylococcus aureus and Escherichia coli. The incorporation of nitrogen chromophores and halogen into vanillin moieties improved binding interactions and binding affinity.