Background: Infectious disease is increasingly hampering human health, which challenge
the discovery of new antibacterial target. Peptide deformylase (PDF), a metalloenzyme responsible for
catalyzing the removal of the N-formyl group from nascent proteins, was considered as an important
target in antibacterial drug discovery.
Objective: Reported here are the design, synthesis and biological evaluation of vanillin hydroxamic
Methods and Results: Analysis of the structure-activity relationships lead to the discovery of compound
8, which exhibits promising antibacterial activity against Escherichia coli, Staphylococcus
aureus, Aspergillus oryzae, and Aspergillus foetidus with the MIC value of 0.32 µg/ml, 0.32 µg/ml,
0.16 µg/ml and 0.16 µg/ml, respectively. Furthermore, molecular docking study was applied to elucidate
binding interaction between compound 8 and PDF, which indicate that compound 8 not only
shares the same binding pocket with actinonin, but also has a similar binding pattern. In silico pharmacokinetic
and toxicity prediction studies also suggested that compound 8 has a relatively high drug
score of 0.80, and has no risk of toxicity.
Conclusion: Compound 8 might represent a promising scaffold for the further development of novel