scholarly journals Metabolic pathway rerouting inParaburkholderia rhizoxinicaevolved long-overlooked derivatives of coenzyme F420

2019 ◽  
Author(s):  
Daniel Braga ◽  
Daniel Last ◽  
Mahmudul Hasan ◽  
Huijuan Guo ◽  
Daniel Leichnitz ◽  
...  

AbstractCoenzyme F420is a specialized redox cofactor with a highly negative redox potential. It supports biochemical processes like methanogenesis, degradation of xenobiotics or the biosynthesis of antibiotics. Although well-studied in methanogenic archaea and actinobacteria, not much is known about F420in Gram-negative bacteria. Genome sequencing revealed F420biosynthetic genes in the Gram-negative, endofungal bacteriumParaburkholderia rhizoxinica, a symbiont of phytopathogenic fungi. Fluorescence microscopy, high-resolution LC-MS, and structure elucidation by NMR demonstrated that the encoded pathway is active and yields unexpected derivatives of F420(3PG-F420). Further analyses of a biogas-producing microbial community showed that these derivatives are more widespread in nature. Genetic and biochemical studies of their biosynthesis established that a specificity switch in the guanylyltransferase CofC re-programmed the pathway to start from 3-phospho-D-glycerate, suggesting a rerouting event during the evolution of F420biosynthesis. Furthermore, the cofactor activity of 3PG-F420was validated, thus opening up perspectives for its use in biocatalysis. The 3PG-F420biosynthetic gene cluster is fully functional inEscherichia coli, enabling convenient production of the cofactor by fermentation.


2020 ◽  
Vol 16 (4) ◽  
pp. 481-488
Author(s):  
Heli Sanghvi ◽  
Satyendra Mishra

Background: Curcumin, one of the most important pharmacologically significant natural products, has gained significant consideration among scientists for decades since its multipharmacological activities. 1, 3-Dicarbonyl moiety of curcumin was found to be accountable for the rapid degradation of curcumin molecule. The aim of present work is to replace 1, 3-dicarbonyl moiety of curcumin by pyrazole and phenylpyrazole derivatives with a view to improving its stability and to investigate the role of substitution in N-phenylpyrazole curcumin on its antibacterial activity against both Gram-positive as well as Gram-negative bacteria. Methods: Pyrazole derivatives of curcumin were prepared by heating curcumin with phenyhydrazine/ substituted phenyhydrazine derivatives in AcOH. The residue was purified by silica gel column chromatography. Structures of purified compounds were confirmed by 1H NMR and Mass spectroscopy. The synthesized compounds were evaluated for their antibacterial activity by the microdilution broth susceptibility test method against gram positive (S. aureus) and gram negative (E. coli). Results: Effects of substitution in N-phenylpyrazole curcumin derivatives against S. aureus and E. coli were studied. The most active N-(3-Nitrophenylpyrazole) curcumin (12) exhibits twenty-fold more potency against S. aureus (MIC: 10μg/mL)) and N-(2-Fluoroophenylpyrazole) curcumin (5) fivefold more potency against E. coli (MIC; 50 μg/mL) than N-phenylpyrazole curcumin (4). Whereas, a remarkable decline in anti-bacterial activity against S. aureus and E. coli was observed when electron donating groups were incorporated in N-phenylpyrazole curcumin (4). Comparative studies of synthesized compounds suggest the effects of electron withdrawing and electron donating groups on unsubstituted phenylpyrazole curcumin (4). Conclusion: The structure-activity relationship (SAR) results indicated that the electron withdrawing and electron donating at N-phenylpyrazole curcumin played key roles for their bacterial inhibitory effects. The results of the antibacterial evaluation showed that the synthesized pyrazole derivatives of curcumin displayed moderate to very high activity in S. aureus. In conclusion, the series of novel curcumin derivatives were designed, synthesized and tested for their antibacterial activities against S. aureus and E. coli. Among them, N-(3-Nitrophenylpyrazole curcumin; 12) was most active against S. aureus (Gram-positive) and N-(2-Fluoroophenylpyrazole) curcumin (5) against E. coli (Gram-negative) bacteria.



1999 ◽  
Vol 43 (5) ◽  
pp. 1274-1276 ◽  
Author(s):  
Manhong Wu ◽  
Robert E. W. Hancock

ABSTRACT Both linear and cyclic derivatives of the cyclic 12-amino-acid antimicrobial peptide bactenecin were designed based on optimization of amphipathicity and charge location. In general, increasing the number of positive charges at the N and C termini and adding an extra tryptophan residue in the loop not only increased the activities against both gram-positive and gram-negative bacteria but also broadened the antimicrobial spectrum.



eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Romain Mercier ◽  
Yoshikazu Kawai ◽  
Jeff Errington

The peptidoglycan cell wall is a defining structural feature of the bacterial kingdom. Curiously, some bacteria have the ability to switch to a wall-free or ‘L-form’ state. Although known for decades, the general properties of L-forms are poorly understood, largely due to the lack of systematic analysis of L-forms in the molecular biology era. Here we show that inhibition of peptidoglycan precursor synthesis promotes the generation of L-forms from both Gram-positive and Gram-negative bacteria. We show that the L-forms generated have in common a mechanism of proliferation involving membrane blebbing and tubulation, which is dependent on an altered rate of membrane synthesis. Crucially, this mode of proliferation is independent of the essential FtsZ based division machinery. Our results suggest that the L-form mode of proliferation is conserved across the bacterial kingdom, reinforcing the idea that it could have been used in primitive cells, and opening up its use in the generation of synthetic cells.



Author(s):  
Chinyere Benardette Chinaka Ikpa ◽  
Uchechukwu C. Okoro ◽  
Collins I. Ubochi ◽  
Kieran O. Nwanorh

The 2-phenylsulphonamide derivatives of amino acids were synthesis by simple substitution of benzenesulphonylchloride (6) with amino acids (1-5) containing pharmacological active functionalities. Structures of the synthesised compounds (7a-7e) were characterised using FT-IR, NMR(1H,13C) and elemental analysis. The anti bacterial activities of the synthesised compounds were evaluated against gram positive bacteria: Staph and Streptococcus, gram negative bacteria: E-coli, Klebsiella, Proteus, and pseudomonas using 200 µl of 10 mg/ml and minimum inhibitory concentration (MIC) were also determined. The compounds exhibited effective anti bacterial properties though some are not more active than the standard drug ciprofloxacin.



Author(s):  
Shipra Baluja ◽  
Nilesh Godvani ◽  
Sumitra Chanda

In this work, some novel derivatives of Cyanopyridines and Isoxazoles were synthesized using Vilsmeier-Haack reagent and their structures were confirmed by FTIR, 1H NMR and mass spectroscopic methods. The antibacterial activities of these synthesized compounds were studied in DMSO and DMF by agar well diffusion method against some Gram positive and Gram negative bacteria. It is observed that activity depends upon three S: solvent, strain and structure.



2018 ◽  
Vol 22 (2) ◽  
pp. 267-271
Author(s):  
V.G. Paliy ◽  
I.G. Paliy ◽  
A.O. Dudar ◽  
D.V. Paliy ◽  
A. V. Kulyk

Successful research by scientists of new synthetic substances of various chemical groups contributes to the broadening of the arsenal of antimicrobial drugs for the prevention and treatment of purulent-inflammatory diseases. Antimicrobial drugs, as a rule, suppress pathogenic, invasive, adhesive properties and reduce the resistance of microorganisms to antibiotics in pathogens of supportive inflammatory diseases; significantly increase the effectiveness of treatment of diseases of infectious origin. The purpose of the study was to study the physicochemical, antimicrobial properties of derivatives of menthol, phenol and quinoline. The results of the study of physicochemical, antimicrobial properties of six chemical compounds of menthol, quinoline, and phenol derivatives using the principle of complex research, in which physicochemical, microbiological methods were used, are presented. There was shown that quaternary ammonium compounds of the menthol derivatives were alike white powders with a molecular weight of 581–693, a melting point of 990 to 1850° C. The chemicals are soluble in water, ethanol. Quinoline preparations have a molecular weight of 687; 756, melting point 178–2000°C; dissolved in ethanol. Compounds of phenol had a molecular weight of 111, 112, a melting point of 1020, 1100°C was soluble in ethanol. It has been established that synthesized substances possess a wide spectrum of antimicrobial action on Gram-positive, Gram-negative bacteria, Candida albicans. In antibiotic resistant strains of Staphylococci no markers of resistance to drugs containing in the molecule menthol, phenol, quinoline were found. In complex physical and chemical systems, it was important to study the coefficient of surface tension of solutions of drugs, which was an important objective physical indicator of the molecular state of various drugs. Distilled water was used as a control. Experiments were performed according to a well-known technique. According to the results of the study, in the control the surface tension of water was it was found to be 55,70 dn/cm2. In an experiment with 0,1% solution of decamethoxin; the drug number 2 was 40,80 dn/cm2 and 38,20 dn/cm2. In derivatives of quinoline (DN, drug № 4), was 39,60 dn/cm2 and 34,50 dn/cm2. Solutions of phenol (preparations №5; №6) were characterized by surface tension 32,40–43,50 dn/cm2. Surface tension of solutions of preparations depended on their chemical structure. The antimicrobial properties of the preparations were determined on the museum and clinical strains of microorganisms, which had typical tynctorial, morphological, and cultural characteristics. For a complete biological characterization in strains of Staphylococci, the formation of coagulase enzymes, lecithovitellase, hemolysins, and mannitol fermentation in anaerobic conditions were studied. At 12 museum and clinical strains of bacteria, bacteriostatic and bactericidal effects of six drugs, which are derivatives of menthol (DK, №2), quinoline (DN, №4), phenol (preparations №5, №6), have been detected. Derivatives of menthol acted bactericidal to Staphylococci at doses of 0,48-3,9 μg/ml; Quinoline derivatives in the range of 7,8–15,6 μg/ml; derivatives of phenol 31,25–62,5 μg/ml, respectively. Staphylococci were highly resistant to phenol derivatives (31,25–62,5 μg/ml). Gram-negative bacteria exhibited high resistance to quinoline and phenol derivatives (250–500 μg/ml). Summing up the results of determining the antimicrobial action of antiseptics derivatives of menthol, quinoline, it should be emphasized that the drugs have high activity in relation to Staphylococci (0,24–7,8 μg/ml). Phenol derivatives have low bacteriostatic and bactericidal effects on Gram-negative bacteria (125–500 μg/ml), which limits their use in medicine.



2019 ◽  
Vol 35 (4) ◽  
pp. 1248-1253
Author(s):  
Lubna Swellmeen ◽  
Amal Uzrail ◽  
Rand Shahin ◽  
Yusuf AL-Hiari

Fluoroquinolones are well known to have an anti-infective action. In the present study we described the synthesis of novel florouquinolones derivative as antimicrobial agent. The biological test highlighted a good inhibitory activity for the 7-Chloro-1-Alkyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derived synthons especially against pathogenic Gram-negative bacteria (Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Streptococcus agalactiae). The binding interactions were monitored and could explain the good inhibitory activity of the synthesized derivatives of florouquinolones.



2015 ◽  
Vol 2015 ◽  
pp. 1-6
Author(s):  
Mouna Bouzid ◽  
Raed Abdennabi ◽  
Mohamed Damak ◽  
Majed Kammoun

This paper describes the synthesis of a series of dihydroisoquinoline nitrones by isomerization of the corresponding oxaziridines. Nitrones4a–cwere obtained in excellent yields and high purity by a simple and effective method from the isomerization of oxaziridines. The synthesized compounds were also evaluated for their antibacterial activity against Gram-positive and Gram-negative bacteria and fungus.



2017 ◽  
Vol 9 (2) ◽  
pp. 45 ◽  
Author(s):  
Bahareh Behmaram ◽  
Naser Foroughifar ◽  
Neda Foroughifar ◽  
Sara Hallajian

The synthesis of some 1,3-diazoles and thiazoles was realized in different conditions:a) In the presence of PTSA or sulfuric acid as catalyst we obtained only diazole products(4a-d).b) In basic medium such as DABCO or sodium hydroxide and ionic liquid afforded thiazoles.c) Both products, diazoles and thiazoles were collected when using methanol as catalyst and solvent.All structures were confirmed by IR, 1H NMR and 13C NMR spectroscopy. The antibacterial activity of some synthesized compounds was investigated against Escherichia Coli (ATCC: 25922) and Serratia marcescens (ATCC: 13880) as gram negative bacteria, Bacillus sabtilis (ATCC: 6633) and Staphylococcus aureus (ATCC: 6338) as gram positive bacteria. Some of these products exhibit good activities to significant antibacterial activity.



2008 ◽  
Vol 5 (4) ◽  
pp. 963-968 ◽  
Author(s):  
Sabir Hussain ◽  
Jyoti Sharma ◽  
Mohd Amir

Various 4-amino-2-[4-(4-substituted phenyl)-5-sulfanyl-4H-1,2,4-triazol-3-yl] phenol (4a-c), 4-amino-2-{4-amino-5-[(4-substituted phenyl)amino]-4H-1,2,4-triazol-3-yl} phenol (5a-c) and 4-amino-2-{5-[(4-substituted phenyl)amino]-1,3,4-thiadiazole-2-yl} phenol (6a-g) were synthesized and evaluated for their antibacterial and antifungal activity. The compounds showed significant antibacterial activity againstS. aureus(gram-positive) andE.coli(gram-negative) bacteria and antifungal activity againstA. nigerfungi using cup plate technique



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