Antimicrobial activity of DW286 against Streptococcus pneumoniae

Park, Hee Soo; Jung, Sung Ji; Choi, Dong-Rack; Kwak, Jin‐Hwan

doi:10.1016/j.ijantimicag.2010.04.007

Cited by 3 publications

(5 citation statements)

References 14 publications

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“…From the results attained, the MIC values of the compound were significant and are within the range of previously reported MICs by Park et al . () and Tsao and Yin ().…”

Section: Resultsmentioning

confidence: 99%

Bioactive compound fromAspergillus terreusDMTMGK004 synergistically contributes towards potential anti-pathogenicity

Krishnamoorthy

Kannan

Murugan

2018

Lett Appl Microbiol

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This study focused on the evaluation of fungal compound for their anti-pathogenic potential against respiratory pathogens. Soil samples were collected from various geographical regions in Madurai, fungal strain was isolated and identified as Aspergillus terreusDMTMGK004 (MGK004). Secondary metabolites were extracted and evaluated for antioxidant potential. It exhibited significantly high anti-proliferative property against gastric adenocarcinoma (AGS) cell lines. Antimicrobial activity against Gram positive (Streptococcus pneumoniae) and Gram negative (Klebsiella pneumoniae and Haemophilus influenzae) respiratory pathogens were analysed and the minimum inhibitory concentration (MIC) values were determined. Furthermore, the time-killing assay illustrated that the metabolite eliminates 50% of the vegetative cells within few hours of the treatment. From the spectral data, the major functional groups present in the compound were determined as carbonyl group and phenolic hydroxyl group which contribute towards its bioactivity. The compound significantly depreciates the production of extracellular polysaccharides which results in the weakening of biofilm architecture and resistance towards serum killing and phagocytosis. It also induced cell membrane damage which leads to protein and nucleic acid leakage. Hence, the results of the present study could provide a better insinuation towards the formulation of new drug targeting respiratory pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: The ubiquitous fungi Aspergillus terreus is well known for its secondary metabolite production. The fungus was evaluated for production of antagonistic molecule to reduce the growth of infectious agents causing respiratory infections. It exhibited the biological means of antioxidant, anti-proliferative and anti-pathogenic compound production. The compound exhibits killing effect against respiratory pathogens within two hours. It induced cell membrane damage leading to protein and nucleic acid leakage. It significantly reduced the production of extracellular polysaccharides. The results provide needed information to design innovative strategies for targeting pathogenic factors of the respiratory pathogens instead of killing it precisely.

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“…From the results attained, the MIC values of the compound were significant and are within the range of previously reported MICs by Park et al . () and Tsao and Yin ().…”

Section: Resultsmentioning

confidence: 99%

Bioactive compound fromAspergillus terreusDMTMGK004 synergistically contributes towards potential anti-pathogenicity

Krishnamoorthy

Kannan

Murugan

2018

Lett Appl Microbiol

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“…: 71-73 ºC. 1 Methylation of 2 was carried out with a yield of 84 %, but we were not able to obtain the desired products in direct reduction of both functional groups by LiAlH4, or only reduction of ketone moiety of the cyano ketone (3) by NaBH4 in acceptable yields (40-50 %), even when column chromatography separation technique was used. Also, protection of the carbonyl group of 3 by ketalization with diols such as glycol and neopentylglycol, etc.…”

Section: N-tert-butoxycarbonyl-3-cyano-3-methyl-4-oxopyrrolidine (3)mentioning

confidence: 94%

“…Melting points were determined in open capillaries and uncorrected. 1 H NMR spectra were determined on a Varian Mercury-400 spectrometer in DMSO-d6 or CDCl3 using tetramethylsilane as an internal standard. Electrospray ionization mass spectra and high resolution mass spectra were obtained on a MDSSCIEX Q-Tap mass spectrometer and AccuTOF CS JMS-T100CS (JEOL) mass spectrometer, respectively.…”

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confidence: 99%

A Convenient Way to Prepare the Key Intermediate 3-Aminomethyl-3-methyl-4-(metho-xyimino)pyrrolidine Dihydrochloride of DW286, a New Naphthyridone Antibacterial

Feng¹,

Liu²,

Lv³

et al. 2013

Asian J. Chem.

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DW286, a methyl analog of fluoronaphthyridone antibacterial agent gemifloxacin, has completed Phase I clinical trial. Compared with gemifloxacin, DW286 shows better in vitro and in vivo activity against commonly pathogens in clinic, especially Gram-positive resistant bacteria 1-5. However, the current synthetic process of DW286 is rather complex (16 steps in all), involving some reaction steps with high material cost, high production expenses and column chromatography separation techniques 6. We have previously reported a new route and successfully synthesized DW286 by direct condensation of the naphthyridone nucleus 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4dihydro[1,8]naphthyridine-3-carboxylic acid and the sidechain compound 3-(aminomethyl)-4-(methoxyimino)-3methylpyrrolidine dihydrochloride 1 (Scheme-I). As the key intermediate (1) of DW286, it was prepared via a 9-step sequence. In other word, N-Boc-3-cyano-4-oxopyrrolidine (2) was first obtained by one-pot method from glycine ethyl ester hydrochloride and acrylonitrile as starting materials and then methylation, reduction of ketone moity by NaBH4, hydrogenation of the cyano group, Jones oxidation, oximation and deprotection gave compound 1 7. However, the preparation of 1 was not suitable for industrial application due to the following reasons 1) heavy metal (Cr) pollution; 2) use of column chromatography separation techniques. On the basis of the above considerations, we have recently focused on improving the synthetic route of the key intermediate 1. From the cyano ketone (2), the title compound 1 was NOTE

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“…QRDR sequences in gyrA , gyrB , parC, and parE were amplified by polymerase chain reaction (PCR) using primers described previously [18]. PCR products were purified using AccuPrep™ PCR Product Purification Kit (Bioneer Co. Ltd., Daejeon, Korea), and then sequenced using a system from Solgent Co. Ltd. (Daejeon, Korea).…”

Section: Methodsmentioning

confidence: 99%

“…Mice studies were performed as described previously [18]. S. pneumoniae strain was cultured in tryptic soy agar medium (Difco) supplemented with 5% defibrinated sheep blood at 35 °C for 18 h. For inoculation, S. pneumoniae 1065 was suspended in 0.9% NaCl.…”

Section: Methodsmentioning

confidence: 99%

Antimicrobial Activity of Zabofloxacin against Clinically Isolated Streptococcus pneumoniae

Park

Kim

et al. 2016

Molecules

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Abstract:Zabofloxacin is a novel fluoroquinolone agent that has potent activity against gram-positive pathogens. In this study, we confirmed that zabofloxacin showed the most potent in vitro and in vivo activities against drug-resistant Streptococcus pneumoniae. Among the fluoroquinolone compounds, zabofloxacin showed the most potent in vitro activity against clinical isolates of penicillin-sensitive S. pneumoniae (minimum inhibitory concentration, MIC 90 : 0.03 mg/L) and penicillin-resistant S. pneumoniae (MIC 90 : 0.03 mg/L). Against quinolone-resistant S. pneumoniae, zabofloxacin (MIC 90 : 1 mg/L) was more active than ciprofloxacin, sparfloxacin, and moxifloxacin; however, its activity was the same as that of gemifloxacin. The in vivo activity of zabofloxacin was most potent among the quinolone compounds tested against the systemic infection and respiratory tract infection models in mice.

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Antimicrobial activity of DW286 against Streptococcus pneumoniae

Cited by 3 publications

References 14 publications

Bioactive compound fromAspergillus terreusDMTMGK004 synergistically contributes towards potential anti-pathogenicity

Bioactive compound fromAspergillus terreusDMTMGK004 synergistically contributes towards potential anti-pathogenicity

A Convenient Way to Prepare the Key Intermediate 3-Aminomethyl-3-methyl-4-(metho-xyimino)pyrrolidine Dihydrochloride of DW286, a New Naphthyridone Antibacterial

Antimicrobial Activity of Zabofloxacin against Clinically Isolated Streptococcus pneumoniae

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