Abstract
As part of a project to characterise plant-derived natural products that modulate bacterial 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 cis 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 μg/ml. Incorporation of 1 and 2 into the growth medium at 10 μg/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 IC 50 of 50 μM, 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.
Published Version
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