In vitro and ex vivo activity of peptide deformylase inhibitors against Mycobacterium tuberculosis H37Rv

Sharma, Anshika; Sharma, Sadhna; Khuller, G. K.; Kanwar, A.J.

doi:10.1016/j.ijantimicag.2009.04.005

Cited by 18 publications

(14 citation statements)

References 38 publications

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“…NHF165 exhibited the highest activity against V. anguillarum , and the functional component was finally determined as actinonin. Actinonin was isolated from soil Streptomyces in 1962 and was reported to be an inhibitor targeting E. coli PDF and M. tuberculosis PDF ( Sharma et al, 2009 ). Our discovery is the first report to show that marine derived actinonin possesses anti- Vibrio activity via targeting VaPDF.…”

Section: Discussionmentioning

confidence: 99%

“…The widespread occurrence, conservation, and essential nature of deformylase in bacteria make it an attractive target for antibacterial drug discovery ( Giglione et al, 2000 ; Sangshetti et al, 2015 ). PDF is widely used in human bacteria infection treatment caused by Staphylococcus aureus, Streptococcus pneumonia, Helicobacter pylori , Haemophilus influenza and Mycobacterium tuberculosis , etc ( Sharma et al, 2009 ; Peyrusson et al, 2015 ). PDF inhibitors, GSK-1322322, BB-83698 and LBM-415, have entered into clinical developments ( Sangshetti et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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The Inhibition and Resistance Mechanisms of Actinonin, Isolated from Marine Streptomyces sp. NHF165, against Vibrio anguillarum

Yang

Sun

2016

Front. Microbiol.

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Vibrio sp. is the most serious pathogen in marine aquaculture, and the development of anti-Vibrio agents is urgently needed. However, it is extreme lack of high-throughput screening (HTS) model for searching anti-Vibrio compounds. Here, we established a protein-based HTS screening model to identify agents targeting peptide deformylase (PDF) of Vibrio anguillarum. To find potential anti-Vibrio compounds, crude extracts derived from marine actinomycetes were applied for screening with this model. Notably, crude extract of strain Streptomyces sp. NHF165 inhibited dramatically both on V. anguillarum PDF (VaPDF) activity and V. anguillarum cell growth. And actinonin was further identified as the functional component. Anti-VaPDF and anti-V. anguillarum activities of actinonin were dose-dependent, and the IC50 values were 6.94 and 2.85 μM, respectively. To understand the resistance of V. anguillarum against actinonin, spontaneous V. anguillarum mutants with resistance against actinonin were isolated. Surprisingly, for the resistant strains, the region between 774 and 852 base pairs was found to be absent in the gene folD which produces 10-formyl-tetrahydrofolate, a donor of N-formyl to Met-tRNAfmet. When compared to the wild type strain, ΔfolD mutant showed eight times of minimum inhibition concentration on actinonin, however, the folD complementary strain could not grow on the medium supplemented with actinonin, which suggested that folD gene mutation was mainly responsible for the actinonin resistance. To our knowledge, this is the first report showing that marine derived Streptomyces sp. could produce actinonin with anti-VaPDF activity and the resistance against actinonin by V. anguillarum is mediated by mutation in folD gene.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Inhibition and Resistance Mechanisms of Actinonin, Isolated from Marine Streptomyces sp. NHF165, against Vibrio anguillarum

Yang

Sun

2016

Front. Microbiol.

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“…Molecular docking has been used for the screening of potent drug molecules by targeting the aerolysin of A. hydrophila [38] and 3-oxoacyl-acyl carrier protein synthase II of Mycobacterium tuberculosis [56]. Sharma et al [57] have tested BB-3497 and actinonin and both were found to be potent drugs against the PDF of M. tuberculosis at low concentrations. While in the case of interaction of a BBS-02 molecule with PDF, a number of amino acids including Tyr39, Ile45, Gly46, Gln51, Leu92, His137, Glu134, Cys91, Gly90, Ile120, and Leu92 were obtained (Figure 5a).…”

Section: Screening Of Potent Drugs and Phylogenetic Analysismentioning

confidence: 99%

A Potential Screening of Peptide Deformylase Inhibitors Towards the Control of Aeromonas hydrophila

Singh¹,

Mani²

2017

Curr Synthetic Sys Biol

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Currently, the prevalence of multidrug resistance Aeromonas hydrophila is one of the major issues and challenges for aquatic and terrestrial organisms. Therefore, an urgent need arises to control it using a potent and specific drug. Here, we identified a peptide deformylase (PDF) in A. hydrophila, which is a ubiquitous enzyme and one of the most attractive drug targets. We used the PDF protein sequences for generating a 3-D model using homology modeling. The 3-D model was validated and it was found 91% of the present amino acids in allowed regions of the Ramachandran plot. We used the 3-D model of PDF for the screening of drugs through molecular docking and found BB-3497, actinonin, and BBS-02 were more potent than other studied drugs based on binding energy. We have also generated a phylogenetic tree of PDF from A. hydrophila with other homologous bacteria, suggesting that similar drugs could also be applied to the control of those bacteria. These findings provide a new insight for the better understanding of PDF, which is a novel target for the development of more potent inhibitors towards the better control of multidrug resistant A. hydrophila.

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“…[32,33] 1,10-Phenanthroline has been found active against Mycobacterium tuberculosis. [34] Tuberculosis is a well-known disease that has troubled human beings in past times [35] and still remains a major health problem. The World Health Organization (WHO) estimates that one-third of the population is infected with latent Mycobacterium tuberculosis and approximately 3 million people per year die due to this bacillus.…”

Section: Introductionmentioning

confidence: 99%

Spectral, thermal, biological and multi‐heating rate kinetic properties of Cu(II) complexes containing N₂O₂ donor ligands: 1,10‐phenanthroline and acyl coumarins

Patel

Dholariya

Patel

et al. 2012

Applied Organom Chemis

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A series of newly synthesized coumarin‐based mixed‐ligand copper complexes with 1,10‐phenanthroline (Ph) were investigated by means of thermogravimetry, differential thermogravimetry, differential scanning calorimetry (DSC), electronic spectra and magnetic measurements. Structural and spectroscopic properties of neutral bidentate ligands as well as all complexes were studied on the basis of mass spectra, NMR (1H and 13C) spectra, FT‐IR spectrophotometry and elemental analyses. IR spectral data suggest tetra‐coordinated N2O2 bonding of ligand toward metal ion. Dynamic scan of DSC experiments for copper complexes were obtained at different heating rates (2.5–20°C min−1). Isoconversion methods of Kissinger and Ozawa were used for the determination of the pre‐exponential factor (A), activation energy (Ea) and order of reaction (n). Kinetic parameters for second‐step degradation obtained by Kissinger's and Ozawa's methods are in good agreement. The results indicate that complexes are much stronger free radical scavenger and antioxidant compounds than ligands. Antimycobacterial screening of ligand and its copper compound against Mycobacterium tuberculosis shows clear enhancement in antitubercular activity upon copper complexation. Also good antimicrobial activities of the complexes against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Salmonella typhus, Aspergillus niger, Candida albicans and Aspergillus clavatus have been found compared to its free ligands. Copyright © 2012 John Wiley & Sons, Ltd.

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In vitro and ex vivo activity of peptide deformylase inhibitors against Mycobacterium tuberculosis H37Rv

Cited by 18 publications

References 38 publications

The Inhibition and Resistance Mechanisms of Actinonin, Isolated from Marine Streptomyces sp. NHF165, against Vibrio anguillarum

The Inhibition and Resistance Mechanisms of Actinonin, Isolated from Marine Streptomyces sp. NHF165, against Vibrio anguillarum

A Potential Screening of Peptide Deformylase Inhibitors Towards the Control of Aeromonas hydrophila

Spectral, thermal, biological and multi‐heating rate kinetic properties of Cu(II) complexes containing N₂O₂ donor ligands: 1,10‐phenanthroline and acyl coumarins

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In vitro and ex vivo activity of peptide deformylase inhibitors against Mycobacterium tuberculosis H37Rv

Cited by 18 publications

References 38 publications

The Inhibition and Resistance Mechanisms of Actinonin, Isolated from Marine Streptomyces sp. NHF165, against Vibrio anguillarum

The Inhibition and Resistance Mechanisms of Actinonin, Isolated from Marine Streptomyces sp. NHF165, against Vibrio anguillarum

A Potential Screening of Peptide Deformylase Inhibitors Towards the Control of Aeromonas hydrophila

Spectral, thermal, biological and multi‐heating rate kinetic properties of Cu(II) complexes containing N2O2 donor ligands: 1,10‐phenanthroline and acyl coumarins

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Product

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Spectral, thermal, biological and multi‐heating rate kinetic properties of Cu(II) complexes containing N₂O₂ donor ligands: 1,10‐phenanthroline and acyl coumarins