scholarly journals Design, docking, synthesis and anti E. coli screening of novel thiadiazolo thiourea derivatives as possible inhibitors of Enoyl ACP reductase (FabI) enzyme

2014 ◽  
Vol 9 (1) ◽  
Author(s):  
Sonia George ◽  
Mohammed Basheer Ramzeena ◽  
Sayee Vignesh Ram ◽  
Senthil Kumar Selvaraj ◽  
Shinu Rajan ◽  
...  
Keyword(s):  
Thiourea Derivatives ◽  
E Coli ◽  
Enoyl Acp Reductase

scholarly journals Synthesis and Bacteriostatic Activities of Bis(thiourea) Derivatives with Variable Chain Length

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Ainaa Nadiah Abd Halim ◽  
Zainab Ngaini
Keyword(s):  
Chain Length ◽  
Alkyl Chain ◽  
Binding Free Energy ◽  
Kinetic Method ◽  
Antibacterial Properties ◽  
Thiourea Derivatives ◽  
E Coli ◽  
Excellent Activity ◽  
Enoyl Acp Reductase ◽  
Long Alkyl Chain

A series of 1,4-bis(decoxyphenyl)carbamothioyl-terephthalamide derivatives was successfully synthesised by reaction of benzene-1,4-dicarbonyl isothiocyanate intermediates with long alkyl chain. The alkylation was performed via Williamson etherification of 4-acetamidophenol with bromoalkanes. The synthesised bis(thiourea) derivatives differed in the chain length, CnH2n+1, wheren=10, 12, and 14. The structures of all compounds were characterised by elemental CHN analysis, IR,1H, and13C NMR spectroscopies. Bacteriostatic activities of bis(thiourea derivatives which consisted of two folds of N-H, C=O, and C=S and long alkyl chain substituents were carried out against Gram-negative bacteria (Escherichia coli, ATCC 25922) via turbidimetric kinetic method. Bis(thiourea) derivatives withn=10andn=12displayed excellent activity againstE. coliwith MIC of 135 µg/mL and 145 µg/mL, respectively, while bis(thiourea) derivatives withn=14acted as cutoff point with no antibacterial properties. Similar trend was observed in binding affinity to the active site of enoyl ACP reductase (FabI), which demonstrated binding free energy of-5.3 Kcal/mol and-4.9and-4.8 Kcal/mol, respectively.

scholarly journals Synthesis, Antimicrobial Activity and Molecular Docking of Novel Thiourea Derivatives Tagged with Thiadiazole, Imidazole and Triazine Moieties as Potential DNA Gyrase and Topoisomerase IV Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2766 ◽  
Author(s):  
Heba E. Hashem ◽  
Abd El-Galil E. Amr ◽  
Eman S. Nossier ◽  
Elsayed A. Elsayed ◽  
Eman M. Azmy
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Topoisomerase Iv ◽  
Thiourea Derivatives ◽  
E Coli ◽  
Cytotoxicity Studies ◽  
Ic50 Values

To develop new antimicrobial agents, a series of novel thiourea derivatives incorporated with different moieties 2–13 was designed and synthesized and their biological activities were evaluated. Compounds 7a, 7b and 8 exhibited excellent antimicrobial activity against all Gram-positive and Gram-negative bacteria, and the fungal Aspergillus flavus with minimum inhibitory concentration (MIC) values ranged from 0.95 ± 0.22 to 3.25 ± 1.00 μg/mL. Furthermore, cytotoxicity studies against MCF-7 cells revealed that compounds 7a and 7b were the most potent with IC50 values of 10.17 ± 0.65 and 11.59 ± 0.59 μM, respectively. On the other hand, the tested compounds were less toxic against normal kidney epithelial cell lines (Vero cells). The in vitro enzyme inhibition assay of 8 displayed excellent inhibitory activity against Escherichia coli DNA B gyrase and moderate one against E. coli Topoisomerase IV (IC50 = 0.33 ± 1.25 and 19.72 ± 1.00 µM, respectively) in comparison with novobiocin (IC50 values 0.28 ± 1.45 and 10.65 ± 1.02 µM, respectively). Finally, the molecular docking was done to position compound 8 into the E. coli DNA B and Topoisomerase IV active pockets to explore the probable binding conformation. In summary, compound 8 may serve as a potential dual E. coli DNA B and Topoisomerase IV inhibitor.

scholarly journals Dynamic control over feedback regulatory mechanisms improves NADPH fluxes and xylitol biosynthesis in engineered E. coli

2020 ◽  
Author(s):  
Shuai Li ◽  
Eirik A. Moreb ◽  
Zhixia Ye ◽  
Jennifer N. Hennigan ◽  
Daniel Baez Castellanos ◽  
...  
Keyword(s):  
Dynamic Control ◽  
List Type ◽  
E Coli ◽  
Ferredoxin Oxidoreductase ◽  
Ferredoxin Reductase ◽  
Enoyl Acp Reductase ◽  
Membrane Bound ◽  
Pyruvate Ferredoxin Oxidoreductase ◽  
Glucose 6 Phosphate Dehydrogenase

AbstractWe report improved NADPH flux and xylitol biosynthesis in engineered E. coli. Xylitol is produced from xylose via an NADPH dependent reductase. We utilize two-stage dynamic metabolic control to compare two approaches to optimize xylitol biosynthesis, a stoichiometric approach, wherein competitive fluxes are decreased, and a regulatory approach wherein the levels of key regulatory metabolites are reduced. The stoichiometric and regulatory approaches lead to a 16 fold and 100 fold improvement in xylitol production, respectively. Strains with reduced levels of enoyl-ACP reductase and glucose-6-phosphate dehydrogenase, led to altered metabolite pools resulting in the activation of the membrane bound transhydrogenase and a new NADPH generation pathway, namely pyruvate ferredoxin oxidoreductase coupled with NADPH dependent ferredoxin reductase, leading to increased NADPH fluxes, despite a reduction in NADPH pools. These strains produced titers of 200 g/L of xylitol from xylose at 86% of theoretical yield in instrumented bioreactors. We expect dynamic control over enoyl-ACP reductase and glucose-6-phosphate dehydrogenase to broadly enable improved NADPH dependent bioconversions.HighlightsDecreases in NADPH pools lead to increased NADPH fluxesPyruvate ferredoxin oxidoreductase coupled with NADPH-ferredoxin reductase improves NADPH production in vivo.Dynamic reduction in acyl-ACP/CoA pools alleviate inhibition of membrane bound transhydrogenase and improve NADPH fluxXylitol titers > 200g/L in fed batch fermentations with xylose as a sole feedstock.

ucFabV Requires Functional Reductase Activity to Confer Reduced Triclosan Susceptibility in Escherichia coli

2015 ◽  
Vol 25 (6) ◽  
pp. 394-402 ◽  
Author(s):  
Taylor L. Fischer ◽  
Robert J. White ◽  
Katherine F.K. Mares ◽  
Devin E. Molnau ◽  
Justin J. Donato
Keyword(s):  
Escherichia Coli ◽  
Reductase Activity ◽  
Acid Synthesis ◽  
Temperature Sensitive ◽  
Wild Type ◽  
E Coli ◽  
Enoyl Acp Reductase ◽  
Selection For

<b><i>Background/Aims:</i></b> We previously identified the Triclo1 fosmid in a functional metagenomic selection for clones that increased triclosan tolerance in <i>Escherichia coli</i>. The active enzyme encoded by Triclo1 is ucFabV. Although ucFabV is homologous to FabV from other organisms, ucFabV contains substitutions at key positions that would predict differences in substrate binding. Therefore, a detailed characterization of ucFabV was conducted to link its biochemical activity to its ability to confer reduced triclosan sensitivity. <b><i>Methods:</i></b> ucFabV and a catalytic mutant were purified and used to reduce crotonoyl-CoA in vitro. The mutant and wild-type enzymes were introduced into <i>E. coli</i>, and their ability to confer triclosan tolerance as well as suppress a temperature-sensitive mutant of FabI were measured. <b><i>Results:</i></b> Purified ucFabV, but not the mutant, reduced crotonoyl-CoA in vitro. The wild-type enzyme confers increased triclosan tolerance when introduced into <i>E. coli</i>, whereas the mutant remained susceptible to triclosan<i>. </i>Additionally, wild-type ucFabV, but not the mutant, functionally replaced FabI within living cells. <b><i>Conclusion:</i></b> ucFabV confers increased tolerance through its function as an enoyl-ACP reductase. Furthermore, ucFabV is capable of restoring viability in the presence of compromised FabI, suggesting ucFabV is likely facilitating an alternate step within fatty acid synthesis, bypassing FabI inhibition.

scholarly journals Triclosan Resistance of Pseudomonas aeruginosa PAO1 Is Due to FabV, a Triclosan-Resistant Enoyl-Acyl Carrier Protein Reductase

2009 ◽  
Vol 54 (2) ◽  
pp. 689-698 ◽  
Author(s):  
Lei Zhu ◽  
Jinshui Lin ◽  
Jincheng Ma ◽  
John E. Cronan ◽  
Haihong Wang
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mutant Strain ◽  
Acyl Carrier Protein ◽  
Acid Synthesis ◽  
Carrier Protein ◽  
Active Efflux ◽  
E Coli ◽  
Genes Encoding ◽  
Enoyl Acp Reductase ◽  
Triclosan Resistance

ABSTRACT Triclosan, a very widely used biocide, specifically inhibits fatty acid synthesis by inhibition of enoyl-acyl carrier protein (ACP) reductase. Escherichia coli FabI is the prototypical triclosan-sensitive enoyl-ACP reductase, and E. coli is extremely sensitive to the biocide. However, other bacteria are resistant to triclosan, because they encode triclosan-resistant enoyl-ACP reductase isozymes. In contrast, the triclosan resistance of Pseudomonas aeruginosa PAO1 has been attributed to active efflux of the compound (R. Chuanchuen, R. R. Karkhoff-Schweizer, and H. P. Schweizer, Am. J. Infect. Control 31:124-127, 2003). We report that P. aeruginosa contains two enoyl-ACP reductase isozymes, the previously characterized FabI homologue plus a homologue of FabV, a triclosan-resistant enoyl-ACP reductase recently demonstrated in Vibrio cholerae. By deletion of the genes encoding P. aeruginosa FabI and FabV, we demonstrated that FabV confers triclosan resistance on P. aeruginosa. Upon deletion of the fabV gene, the mutant strain became extremely sensitive to triclosan (>2,000-fold more sensitive than the wild-type strain), whereas the mutant strain lacking FabI remained completely resistant to the biocide.

Spiro-naphthyridinone piperidines as inhibitors of S. aureus and E. coli enoyl-ACP reductase (FabI)

2009 ◽  
Vol 19 (18) ◽  
pp. 5355-5358 ◽  
Author(s):  
Peter B. Sampson ◽  
Christine Picard ◽  
Sean Handerson ◽  
Teresa E. McGrath ◽  
Megan Domagala ◽  
...  
Keyword(s):  
E Coli ◽  
Enoyl Acp Reductase

scholarly journals The SYNTHESIS, SCREENING OF NOVEL 1-SUBSTITUTED-3-(4-OXO-2-PHENYLQUINAZOLIN-3(4H)-YL) UREA AND THIOUREA ANALOGUES AS POTENT ANTIBACTERIALS

2019 ◽  
pp. 38-42
Author(s):  
SANDHYA R. DHOKALE ◽  
SNEHAL R. THAKAR ◽  
DEEPALI A. BANSODE ◽  
KAKASAHEB R. MAHADIK
Keyword(s):  
Antibacterial Activity ◽  
Melting Point ◽  
1H Nmr ◽  
Ir Spectrum ◽  
Mass Spectra ◽  
Substitution Pattern ◽  
Thiourea Derivatives ◽  
E Coli ◽  
Capillary Method

Objective: The proposed study is an attempt to determine antibacterial activity of synthesized novel 1-substituted-3-(4-oxo-2-phenylquinazolin-3(4H)-yl) urea and thiourea analogues as potent antibacterials against S. aureus and E. coli bacteria. Methods: The present study reports new series of 1-substituted-3-(4-oxo-2-phenylquinazolin-3(4H)-yl) urea and thiourea derivatives as potent antibacterial agents. Reagents used in the present study were of synthetic grade and solvents were used after distillation. Novel quinazolinone analogues were synthesized by considering substitution pattern, characterization of the synthesized analogues was performed using various techniques like Thin layer chromatography, Melting point, Infrared spectroscopy, Proton NMR spectrometry and Mass spectrometry. TLC of the synthesized analogues was carried out by using (toluene: methanol in the ratio 2:1), melting point was found by open capillary method, IR spectrum was recorded on JASCO V-530, 1H NMR was recorded on Bruker Avance Spectrometer and Mass spectra were obtained from G6460A, triple quadrupole/MS/MS system. In vitro antibacterial activity was performed against S. aureus and E. coli. Results: Six derivatives of quinazolinone analogues were synthesized. The structures of 1-substituted-3-(4-oxo-2-phenylquinazolin-3(4H)-yl) urea and thiourea derivatives were confirmed by physical and spectral analysis. Synthesized molecules showed Rf of 0.45-0.80 in toluene: methanol mobile phase, melting point was carried out by open capillary method and were in range of 90-210 ° C, IR spectrum was recorded in range of 14000-400 cm-1and showed characteristic peaks of NH and of C-O-NH, 1H NMR of the compounds was distinct to confirm structures with delta values in the range of 7.53-11.960, Mass spectra proved parent peaks of synthesized compounds confirming molecular weight. The compounds were assayed for antibacterial activity against S. aureus and E. coli using ciprofloxacin as standard. The synthesized analogues have shown good yield and comparable antibacterial. Conclusion: The present study delivers a convenient and efficient protocol for the quinazolinone analogues synthesis.

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