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doi:10.1016/j.bmc.2006.08.038 
Copyright © 2006 Elsevier Ltd All rights reserved.
New bisanthraquinone antibiotics and semi-synthetic derivatives with potent activity against clinical Staphylococcus aureus and Enterococcus faecium isolates
Received 1 August 2006;
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Abstract
The escalation of antibiotic resistance among Gram-positive pathogens presents increasing treatment challenges and requires the development of innovative therapeutic agents. Here, we present the antimicrobial properties of structurally unusual bisanthraquinone metabolites produced by a marine streptomycete and four semi-synthetic derivatives. Biological activities were measured against clinically derived isolates of vancomycin-resistant Enterococcus faecium (VRE), and methicillin-susceptible, methicillin-resistant, and tetracycline-resistant Staphylococcus aureus (MSSA, MRSA, and TRSA, respectively). The most potent antibiotic displayed MIC50 values of 0.11, 0.23, and 0.90 μM against a panel (n = 25 each) of clinical MSSA, MRSA, and VRE, respectively, and was determined to be bactericidal by time-kill analysis.
Keywords: Antibiotics; Marine streptomycete; Semi-synthesis; Bisanthraquinone
Article Outline
- 1. Introduction
- 2. Results
- 2.1. Isolation and characterization of bisanthraquinone metabolites
- 2.2. Semi-synthesis of bisanthraquinone analogues
- 2.3. Biological activities of bisanthraquinone analogues
- 3. Discussion
- 4. Experimental
- 4.1. General
- 4.1.1. Isolation and fermentation of marine Streptomyces sp.
- 4.1.2. Bioassay-guided isolation of bisanthraquinone metabolites 3 and 4
- 4.1.2.1. Bisanthraquinone derivative 3
- 4.1.2.2. Bisanthraquinone derivative 4
- 4.2. Semi-synthetic derivatives
- 4.2.1. Bisanthraquinone derivative 5
- 4.2.2. Bisanthraquinone derivative 6
- 4.2.3. Bisanthraquinone derivative 7
- 4.2.4. Bisanthraquinone derivative 8
- 4.3. Biological activity and in vitro assay
- 4.3.1. Susceptibility testing
- 4.3.2. In vitro time-kill assay
- 4.3.3. Activity defined
- 4.3.4. MIC increase
- Acknowledgements
- Supplementary data
- References
3 log10 CFU/mL reduction in colony count from the initial inoculum, while bacteriostatic activity is defined as a <3-log10 reduction. Inactive is defined as no reduction in CFU/mL.