Background: In recent years, Staphylococcus aureus have developed resistance to
medicines used for the treatment of human infections. Therefore, the search for antibacterial agents
of high potency against Staphylococcus aureus is of great concern. Peptide deformylase (PDF), a
metalloprotease catalyzing the removal of a formyl group from newly synthesized proteins, has been
considered to be an important antibacterial drug target.
Objective: To discover novel antibacterial drugs based on Staphylococcus aureus peptide
Method: PDF-based virtual screening of compounds from Traditional Chinese Medicine
Database@Taiwan was performed by Sybyl X2.1 Surflex dock software. Compounds which possess
high docking score were used for the following antibacterial experiments to evaluate their
antibacterial activities. Kanamycin was also used in the antibacterial experiment as a control
substance in the assay. Furthermore, molecular docking studies was applied to elucidate binding
interaction between some compounds and PDF. In silico pharmacokinetic and toxicity prediction
was explored to explain the reasons why these compounds might stand good chance of providing
some pharmaceutical benefits.
Results: Gentiopicroside, protosappanin B, dihydromyricetin and cryptochlorogenic acid with high
docking score were used for our subsequent antibacterial assays. The Minimum Inhibitory
Concentration (MIC) of kanamycin and gentiopicroside were 0.008 mg·mL-1 and 0.431 mg·mL-1,
respectively, other three compounds, protosappanin B, dihydromyricetin and cryptochlorogenic acid
have close MIC value of 0.50 mg·mL-1.
Conclusion: Dihydromyricetin, with the MIC value of 0.50 mg·mL-1 and relatively high drug score
of 0.82, may serve as a novel antibacterial lead compound.