Synergistic interaction of phenylpropanoids with antibiotics against bacteria.

Phenylpropanoids constitute a large part of our daily diet and there is a possibility that they might interact with synthetic drugs. The present work was aimed at studying the interaction of seven phenylpropanoids (cinnamic, p-coumaric, caffeic, chlorogenic, ferulic, 3,4-dimethoxycinnamic and 2,4,5-trimethoxycinnamic acid) with five antibiotics (amikacin, ampicillin, ciprofloxacin, erythromycin and vancomycin) against Gram-negative (Escherichia coli, Enterobacter aerogenes and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. The interaction studies were performed by chequerboard and time-kill curve assays. Both assays revealed that cinnamic, p-coumaric and ferulic acids were the most active. They combined synergistically with the majority of the antibiotics and exhibited enhanced activity against all the micro-organisms. The time-kill curve parameters were better (P<0.05) for the combinations of amikacin with ferulic, cinnamic or p-coumaric acid than for the individual treatments. Amikacin was the most favourable antibiotic and S. aureus was the most sensitive microbe to most of the combinations. These phenylpropanoids damaged the bacterial membrane as assessed by the LIVE/DEAD BacLight kit, and structure-activity relationship studies indicated that hydrophilic groups enhanced this activity.