3-Shogaol demonstrates antibacterial and antibiotic-potentiating effects against methicillin-resistant Staphylococcus aureus

Aims Shogaols, bioactive compounds derived from ginger (Zingiber officinale), exhibit diverse pharmacological properties. This study evaluated the antibacterial potential of 3-, 4-, 5-, 6-, 7-, 8-, 9-, and 10-shogaols, with emphasis on structure–activity relationships. Methods and Results Antibacterial activity was initially screened against Gram-positive bacteria (methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis) and Gram-negative bacteria (Acinetobacter baumannii and Klebsiella pneumoniae) using disk diffusion assay. Further evaluation against MRSA was performed using broth microdilution and checkerboard assays. Cytotoxicity was assessed in human retinal epithelial (ARPE-19) and human fibroblast (MRC-5) cell lines. Among the tested compounds, only 3-shogaol exhibited measurable antibacterial activity against MRSA. Subsequent analyses focused on 3- and 6-shogaol to evaluate structure–activity relationships and synergistic potential. 3-Shogaol showed better antibacterial activity than 6-shogaol (MIC: 64 µg ml−1 vs. 1024 µg ml−1). Both compounds demonstrated synergistic interactions with amoxicillin, gentamicin, methicillin, and oxacillin against MRSA. However, 3-shogaol produced more frequent and stronger synergistic effects, reflected by lower fractional inhibitory concentration index values. In the cytotoxicity assay, both 3- and 6-shogaol exhibited significantly higher IC50 values compared to the positive control (5-fluorouracil), indicating lower cytotoxicity. Improved selectivity was observed for both 3- and 6-shogaols under synergistic conditions. Conclusion 3-Shogaol is identified as the most bioactive shogaol analogue and demonstrates strong potential as both an antibacterial agent and an antibiotic potentiator against MRSA.