- A Simple and Efficient Flow Preparation of Pyocyanin a Virulence Factor of Pseudomonas aeruginosa
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The synthesis of the naturally occurring toxin pyocyanin has been realized in a short 4 step sequence. The key photochemical reaction and isolation of the final product have been facilitated by the use of flow chemistry techniques and immobilised reagents. Using these procedures gram quantities of pyocyanin were easily prepared in high yield and purity.
- Mortzfeld, Frederik B.,Pietruszka, J?rg,Baxendale, Ian R.
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p. 5424 - 5433
(2019/06/13)
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- Total Syntheses of Pyocyanin, Lavanducyanin, and Marinocyanins A and B
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Total syntheses of pyocyanin, lavanducyanin, and marinocyanins A and B have been accomplished. The N-substituted phenazin-1-one skeleton, a common framework of these natural products, was constructed through the oxidative condensation of pyrogallol with N-substituted benzene-1,2-diamine under an oxygen atmosphere in a single step. Regioselective bromination with N-bromosuccinimide at the C-2 position of N-alkylated phenazin-1-ones afforded brominated natural products.
- Kohatsu, Haruki,Kamo, Shogo,Tomoshige, Shusuke,Kuramochi, Kouji
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p. 7311 - 7314
(2019/10/02)
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- PHENAZINE DERIVATIVES AS ANTIMICROBIAL AGENTS
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The present invention provides novel phenazine derivatives, such as compounds of Formula (I) and (II), and pharmaceutically acceptable salts thereof. The compounds of the invention are expected to be anitmicrobial agents and may act by a microbial warfare strategy (e.g., a reactive oxygen species (ROS)-based competition strategy). The present invention also provides pharmaceutical compositions, kits, uses, and methods that involve the compounds of the invention and may be useful in preventing or treating a microbial infection (e.g., a bacterial infection) in a subject, inhibiting the growth and/or reproduction of a microorganism (e.g., a bacterium), killing a microorganism (e.g., a bacterium), inhibiting the formation and/or growth of a biofilm, or reducing or clearing a biofilm.
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Paragraph 00298-00301
(2015/07/15)
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- Phenazine antibiotic inspired discovery of potent bromophenazine antibacterial agents against Staphylococcus aureus and Staphylococcus epidermidis
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Nearly all clinically used antibiotics have been (1) discovered from microorganisms (2) using phenotype screens to identify inhibitors of bacterial growth. The effectiveness of these antibiotics is attributed to their endogenous roles as bacterial warfare agents against competing microorganisms. Unfortunately, every class of clinically used antibiotic has been met with drug resistant bacteria. In fact, the emergence of resistant bacterial infections coupled to the dismal pipeline of new antibacterial agents has resulted in a global health care crisis. There is an urgent need for innovative antibacterial strategies and treatment options to effectively combat drug resistant bacterial pathogens. Here, we describe the implementation of a Pseudomonas competition strategy, using redox-active phenazines, to identify novel antibacterial leads against Staphylococcus aureus and Staphylococcus epidermidis. In this report, we describe the chemical synthesis and evaluation of a diverse 27-membered phenazine library. Using this microbial warfare inspired approach, we have identified several bromophenazines with potent antibacterial activities against S. aureus and S. epidermidis. The most potent bromophenazine analogue from this focused library demonstrated a minimum inhibitory concentration (MIC) of 0.78-1.56 μM, or 0.31-0.62 μg mL-1, against S. aureus and S. epidermidis and proved to be 32- to 64-fold more potent than the phenazine antibiotic pyocyanin in head-to-head MIC experiments. In addition to the discovery of potent antibacterial agents against S. aureus and S. epidermidis, we also report a detailed structure-activity relationship for this class of bromophenazine small molecules.
- Borrero, Nicholas V.,Bai, Fang,Perez, Cristian,Duong, Benjamin Q.,Rocca, James R.,Jin, Shouguang,Huigens Iii, Robert W.
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supporting information
p. 881 - 886
(2014/02/14)
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