Antibacterials and modulators of bacterial resistance from the immature cones of Chamaecyparis lawsoniana.
As part of an on-going project to characterize compounds from immature conifer cones with antibacterial or modulatory activity against multidrug-resistant (MDR) strains of Staphylococcus aureus, eight compounds were isolated from the cones of Chamaecyparis lawsoniana. The active compounds were mainly diterpenes, with minimum inhibitory concentrations ranging from 4 to 128 microg/ml against MDR effluxing S. aureus strains and two epidemic methicillin-resistant (EMRSA) clinical isolates. The compounds extracted were the diterpenes ferruginol, pisiferol and its epimer 5-epipisiferol, formosanoxide, trans-communic acid and torulosal, the sesquiterpene oplopanonyl acetate and the germacrane 4beta-hydroxygermacra-1(10)-5-diene. Some of these compounds also exhibited modulatory activity in potentiating antibiotic activity against effluxing strains and ferruginol, used at a sub-inhibitory concentration, resulted in an 80-fold potentiation of oxacillin activity against strain EMRSA-15. An efflux inhibition assay using an S. aureus strain possessing the MDR NorA efflux pump resulted in 40% inhibition of ethidium bromide efflux at 10 microM ferruginol (2.86 microg/ml). We report the (1)H and (13)C NMR data for the cis A/B ring junction epimer of pisiferol which we have named 5-epipisiferol. We also unambiguously assign all (1)H and (13)C NMR resonances for trans-communic acid.
Smith
Eileen C J
EC
Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Williamson
Elizabeth M
EM
Wareham
Neale
N
Kaatz
Glenn W
GW
Gibbons
Simon
S
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D029780:Chamaecyparis / Q000033:anatomy & histology* / Q000737:chemistry*; D024881:Drug Resistance, Bacterial; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C075040:NorA protein, Staphylococcus