Antibacterial and resistance modifying activity of Rosmarinus officinalis

As part of a project to characterise plant-derived natural products that modulate bacteria] multidrug resistance (MDR), bioassay-guided fractionation of a chloroform extract of the aerial parts of Rosmarinus officinalis led to the characterisation of the known abietane diterpenes carnosic acid (1), carnosol (2) and 12-methoxy-trans-carnosic acid. Additionally, a new diterpene, the eis A/B ring junction isomer of 12-methoxy-trans-carnosic acid, 12-methoxy-cis-carnosic acid (5), was isolated. The major components were assessed for their antibacterial activities against strains of Staphylococcus aureus possessing efflux mechanisms of resistance. Minimum inhibitory concentrations ranged from 16 to 64 mug/ml. Incorporation of 1 and 2 into the growth medium at 10 mug/ml caused a 32- and 16-fold potentiation of the activity of erythromycin against an erythromycin effluxing strain, respectively. Compound 1 was evaluated against a strain of S. aureus possessing the NorA multidrug efflux pump and was shown to inhibit ethidium bromide efflux with an IC50 of 50 muM, but this activity is likely to be related to the inhibition of a pump(s) other than NorA. The antibacterial and efflux inhibitory activities of these natural products make them interesting potential targets for synthesis. (C) 2004 Elsevier Ltd. All rights reserved.