scholarly journals Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-L-arabinose

2019 ◽  
Author(s):  
Lukáš Kerner ◽  
Paul Kosma
Keyword(s):  
Pathogenic Bacteria ◽  
Ester Group ◽  
Azido Group ◽  
Antimicrobial Drugs ◽  
Dimethyl Methylphosphonate ◽  
Major Mechanism ◽  
Transition State Analogues ◽  
Acid Lactone ◽  
Phosphonate Esters ◽  
Derivatives Of

Incorporation of basic substituents into the structurally conserved domains of cell-wall lipopolysaccharides has been identified as a major mechanism contributing to antimicrobial resistance of Gram-negative pathogenic bacteria. Inhibition of the corresponding enzymatic steps, specifically the transfer of 4-amino-4-deoxy-L-arabinose would thus restore the activity of cationic antimicrobial peptides and several antimicrobial drugs. C-glycosidically linked phospholipid derivatives of  4-amino-4-deoxy-L-arabinose have been prepared as hydrolytically stable and chain-shortened analogues of the native undecaprenyldonor.  The C-phosphonate unit was installed via a Wittig-type reaction of benzyl-protected 1,5-arabinonic acid lactone with the lithium salt of dimethyl methylphosphonate followed by an elimination step of the resulting hemiketal leading to the corresponding exo- and endo-glycal derivatives. The ensuing selective mono-demethylation and hydrogenolysis of the benzyl groups and reduction of the 4-azido group gave the α-L-anomeric arabino- and ribo-configured methyl phosphonate esters. In addition, the monomethyl phosphonate glycal intermediates were converted into n-octyl derivatives followed by subsequent selective removal of the methyl phosphonate ester group and hydrogenation to give the octyl-phosphono derivatives. These intermediates thus will be of value for future conversion into transition state analogues as well as for introduction of various lipid extensions at the anomeric phosphonate moiety.

scholarly journals Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

2020 ◽  
Vol 16 ◽  
pp. 9-14
Author(s):  
Lukáš Kerner ◽  
Paul Kosma
Keyword(s):  
Pathogenic Bacteria ◽  
Ester Group ◽  
Azido Group ◽  
Antimicrobial Drugs ◽  
Dimethyl Methylphosphonate ◽  
Major Mechanism ◽  
Transition State Analogues ◽  
Acid Lactone ◽  
Phosphonate Esters ◽  
Derivatives Of

The incorporation of basic substituents into the structurally conserved domains of cell wall lipopolysaccharides has been identified as a major mechanism contributing to antimicrobial resistance of Gram-negative pathogenic bacteria. Inhibition of the corresponding enzymatic steps, specifically the transfer of 4-amino-4-deoxy-ʟ-arabinose, would thus restore the activity of cationic antimicrobial peptides and several antimicrobial drugs. C-glycosidically-linked phospholipid derivatives of 4-amino-4-deoxy-ʟ-arabinose have been prepared as hydrolytically stable and chain-shortened analogues of the native undecaprenyl donor. The C-phosphonate unit was installed via a Wittig reaction of benzyl-protected 1,5-arabinonic acid lactone with the lithium salt of dimethyl methylphosphonate followed by an elimination step of the resulting hemiketal, leading to the corresponding exo- and endo-glycal derivatives. The ensuing selective monodemethylation and hydrogenolysis of the benzyl groups and reduction of the 4-azido group gave the α-ʟ-anomeric arabino- and ribo-configured methyl phosphonate esters. In addition, the monomethyl phosphonate glycal intermediates were converted into n-octyl derivatives followed by subsequent selective removal of the methyl phosphonate ester group and hydrogenation to give the octylphosphono derivatives. These intermediates will be of value for their future conversion into transition state analogues as well as for the introduction of various lipid extensions at the anomeric phosphonate moiety.

scholarly journals Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Weiwei Wang ◽  
Yan Gao ◽  
Yanting Tang ◽  
Xiaoting Zhou ◽  
Yuezheng Lai ◽  
...  
Keyword(s):  
Rational Design ◽  
Pathogenic Bacteria ◽  
Structural Topology ◽  
Antimicrobial Drugs ◽  
E Coli ◽  
Cytochrome Bd ◽  
Cryo Electron Microscopy ◽  
Functional Mechanisms ◽  
The Relationship ◽  
Potential Oxygen

AbstractCytochromes bd are ubiquitous amongst prokaryotes including many human-pathogenic bacteria. Such complexes are targets for the development of antimicrobial drugs. However, an understanding of the relationship between the structure and functional mechanisms of these oxidases is incomplete. Here, we have determined the 2.8 Å structure of Mycobacterium smegmatis cytochrome bd by single-particle cryo-electron microscopy. This bd oxidase consists of two subunits CydA and CydB, that adopt a pseudo two-fold symmetrical arrangement. The structural topology of its Q-loop domain, whose function is to bind the substrate, quinol, is significantly different compared to the C-terminal region reported for cytochromes bd from Geobacillus thermodenitrificans (G. th) and Escherichia coli (E. coli). In addition, we have identified two potential oxygen access channels in the structure and shown that similar tunnels also exist in G. th and E. coli cytochromes bd. This study provides insights to develop a framework for the rational design of antituberculosis compounds that block the oxygen access channels of this oxidase.

scholarly journals Bacterial Biopolymer: Its Role in Pathogenesis to Effective Biomaterials

Polymers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1242
Author(s):  
Sreejita Ghosh ◽  
Dibyajit Lahiri ◽  
Moupriya Nag ◽  
Ankita Dey ◽  
Tanmay Sarkar ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Carbon Sources ◽  
Chemical Properties ◽  
Interdisciplinary Studies ◽  
Extracellular Dna ◽  
Antimicrobial Drugs ◽  
Cell Factories ◽  
Food Components ◽  
Innovative Biomaterials ◽  
And Chemical Properties

Bacteria are considered as the major cell factories, which can effectively convert nitrogen and carbon sources to a wide variety of extracellular and intracellular biopolymers like polyamides, polysaccharides, polyphosphates, polyesters, proteinaceous compounds, and extracellular DNA. Bacterial biopolymers find applications in pathogenicity, and their diverse materialistic and chemical properties make them suitable to be used in medicinal industries. When these biopolymer compounds are obtained from pathogenic bacteria, they serve as important virulence factors, but when they are produced by non-pathogenic bacteria, they act as food components or biomaterials. There have been interdisciplinary studies going on to focus on the molecular mechanism of synthesis of bacterial biopolymers and identification of new targets for antimicrobial drugs, utilizing synthetic biology for designing and production of innovative biomaterials. This review sheds light on the mechanism of synthesis of bacterial biopolymers and its necessary modifications to be used as cell based micro-factories for the production of tailor-made biomaterials for high-end applications and their role in pathogenesis.

Severe invasive disease caused by hypervirulent Klebsiella pneumoniae: a case report

2021 ◽  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Patient Outcomes ◽  
Liver Abscess ◽  
Pathogenic Bacteria ◽  
Treatment Options ◽  
Invasive Disease ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Antimicrobial Drugs ◽  
Life Threatening

Klebsiella pneumoniae (K. pneumoniae) is a common pathogenic bacteria that causes numerous infectious diseases. Hypervirulent K. pneumoniae (hvKP) can lead to invasive K. pneumoniae liver abscess syndrome, which can induce life-threatening multiple organ dysfunction syndrome or septic shock. We report a case of invasive K. pneumoniae liver abscess syndrome caused by hvKP and discuss the treatment options of this syndrome. Appropriate antimicrobial drugs should be administered to improve prognosis and prevent complications, and laboratory testing is essential to guide clinical management and optimize patient outcomes.

scholarly journals Alkaloid-Rich Crude Extracts, Fractions and Piperamide Alkaloids of Piper guineense Possess Promising Antibacterial Effects

Antibiotics ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 98 ◽  
Author(s):  
Eunice Mgbeahuruike ◽  
Pia Fyhrquist ◽  
Heikki Vuorela ◽  
Riitta Julkunen-Tiitto ◽  
Yvonne Holm
Keyword(s):  
Antibacterial Activity ◽  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Hot Water ◽  
Bacterial Strains ◽  
Inhibitory Effects ◽  
Piper Guineense ◽  
E Coli ◽  
Growth Inhibitory ◽  
Derivatives Of

Piper guineense is a food and medicinal plant commonly used to treat infectious diseases in West-African traditional medicine. In a bid to identify new antibacterial compounds due to bacterial resistance to antibiotics, twelve extracts of P. guineense fruits and leaves, obtained by sequential extraction, as well as the piperine and piperlongumine commercial compounds were evaluated for antibacterial activity against human pathogenic bacteria. HPLC-DAD and UHPLC/Q-TOF MS analysis were conducted to characterize and identify the compounds present in the extracts with promising antibacterial activity. The extracts, with the exception of the hot water decoctions and macerations, contained piperamide alkaloids as their main constituents. Piperine, dihydropiperine, piperylin, dihydropiperylin or piperlonguminine, dihydropiperlonguminine, wisanine, dihydrowisanine and derivatives of piperine and piperidine were identified in a hexane extract of the leaf. In addition, some new piperamide alkaloids were identified, such as a piperine and a piperidine alkaloid derivative and two unknown piperamide alkaloids. To the best of our knowledge, there are no piperamides reported in the literature with similar UVλ absorption maxima and masses. A piperamide alkaloid-rich hexane leaf extract recorded the lowest MIC of 19 µg/mL against Sarcina sp. and gave promising growth inhibitory effects against S. aureus and E. aerogenes as well, inhibiting the growth of both bacteria with a MIC of 78 µg/mL. Moreover, this is the first report of the antibacterial activity of P. guineense extracts against Sarcina sp. and E. aerogenes. Marked growth inhibition was also obtained for chloroform extracts of the leaves and fruits against P. aeruginosa with a MIC value of 78 µg/mL. Piperine and piperlongumine were active against E. aerogenes, S. aureus, E. coli, S. enterica, P. mirabilis and B. cereus with MIC values ranging from 39–1250 µg/mL. Notably, the water extracts, which were almost devoid of piperamide alkaloids, were not active against the bacterial strains. Our results demonstrate that P. guineense contains antibacterial alkaloids that could be relevant for the discovery of new natural antibiotics.

Reaktionsverhalten von β-Oxo-carbonsäurederivaten der Anthracenreihe bei der Synthese von Pyrazolen / On the Reaction Behavior of ß-Oxo Carbonic Acid Derivatives of the Anthracene Series in Pyrazole Synthesis

1999 ◽  
Vol 54 (9) ◽  
pp. 1133-1137
Author(s):  
Astrid Knieß ◽  
Margit Gruner ◽  
Roland Mayer
Keyword(s):  
Carbonyl Group ◽  
Carbonic Acid ◽  
Ester Group ◽  
Reaction Behavior ◽  
Anthracene Derivatives ◽  
Sterical Hindrance ◽  
Derivatives Of

ß-Oxo-1 and 9-anthracenepropionate (6 and 7) reacts with DMF-acetale to enaminones 10 and 11. The reaction of 2-(dimethylamino)methylen-substituted ß-oxo-1 -anthracenepropionate (10) with hydrazines yields 5-(l-anthracenyl)-pyrazol-4-carboxylates (13). In contrast, the cyclocondensation of 3-(9-anthracenyl)-2-(dimethylamino)methylen-3-oxo-propionate (11) with hydrazine hydrochlorides gives 4-(9-anthracenoyl)-5-hydroxy-pyrazoles (14). This is caused by the sterical hindrance of the carbonyl group of the anthracene derivatives in position 9; thus, the cyclocondensation proceeds via reaction of the ester group of the enaminone 11.

Antimicrobial Prophylaxis for Recurrent Acute Otitis Media

1992 ◽  
Vol 101 (1_suppl) ◽  
pp. 33-36 ◽  
Author(s):  
Jack L. Paradise
Keyword(s):  
Native American ◽  
Otitis Media ◽  
Pathogenic Bacteria ◽  
Antimicrobial Prophylaxis ◽  
Acute Otitis Media ◽  
Optimal Dosage ◽  
Antimicrobial Drugs ◽  
American Children ◽  
Long Acting ◽  
Recurrent Otitis Media

Antimicrobial prophylaxis for recurrent otitis media was first reported in 1960 in an uncontrolled study using a long-acting sulfonamide in Native American children younger than 11 years of age. In subsequent controlled studies using various antimicrobial drugs (primarily aminopenicillins or sulfonamides) subjects receiving prophylaxis continued to have episodes of acute otitis media, but at rates substantially lower than those of controls. More recently, prophylaxis has appeared effective in reducing the number of acute recurrences, but not the cumulative proportion of time with middle ear effusion that was present independent of such recurrences. Although questions remain about choice of drug, optimal dosage schedules, risk of untoward drug reactions, duration of use, and the risk of encouraging the emergence of resistant strains of pathogenic bacteria, antimicrobial prophylaxis currently appears to be the most logical first approach in the management of the child with recurrent otitis media.

Immunochemical recognition of phosphate ester derivatives of phenol rings is dependent upon the electronic charge of the ester group

1986 ◽  
Vol 6 (3) ◽  
pp. 265-273 ◽  
Author(s):  
Jane A. Jones ◽  
Alison Wood ◽  
William Cushley
Keyword(s):  
Ph Value ◽  
Ester Group ◽  
Phosphate Esters ◽  
Phosphate Ester ◽  
Electronic Charge ◽  
Alkaline Phosphatases ◽  
Tyrosine Residues ◽  
Substrate Analogues ◽  
Tyrosine Phosphate ◽  
Derivatives Of

The recognition of phosphate and sulphate esters of tyrosine residues has been studied employing antisera with specificity for tyrosine phosphate, and the enzymes aryl sulphatase, and acid and alkaline phosphatases. The ability of tyrosine phosphate, and of phosphate esters of phenol, to inhibit the antiserum was pH dependent. The capacity to effect inhibition appeared to correlate with alterations in the ionisation of the inhibitor. Moreover, the antisera with reactivity for tyrosine phosphate had no reactivity with tyrosine sulphate or sulphate esters of phenol at any pH value studied. The enzymes alkaline phosphatase, acid phosphatase, and aryl sulphatase were also studied. The phosphatases were found not to hydrolyse sulphate ester containing substrate analogues at any pH value in the range 5.0–9.0. In contrast, aryl sulphatase appeared to hydrolyse phosphate esters at pH 5.0 and 7.0, but not at pH 9.0.

Synthesis Antimicrobial and Anticancer Activity of 1-[(arylalkylidene)amino]-3-(4H-1,2,4-triazol-4-yl)thiourea

2014 ◽  
Vol 1 (1) ◽  
pp. 5
Author(s):  
Umasankar Kulandaivelu ◽  
Bhawatha Chawada ◽  
Shireesha Boyapati ◽  
Alavala Rajasekhar Reddy
Keyword(s):  
Antibacterial Activity ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pathogenic Bacteria ◽  
Inhibitory Concentration ◽  
E Coli ◽  
Derivatives Of ◽  
Ht 29 ◽  
Better Than

Arylalkylidene derivatives of aminotriazoles (3a-3j) were synthesized and tested for their antimicrobial and anticancer activity. Four non-pathogenic bacteria [E. coli (NCIM 2068), K. pneumoniae (NCIM 2957), S. aureus (NCIM 2079), B. subtilis (NCIM 2921)] two fungi [C. albicans, A. niger] and two cancer cell lines [HBL-100 and HT-29] were employed in the study. All the compounds were found to have better antibacterial activity against B. subtilis than Ciprofloxacin (standard) and compound 3i was equivalent to Ciprofloxacin in inhibiting S. aureas. Similarly all the compounds inhibited the growth of A. niger better than Fluconazole and compound 3c was equivalent to Fluconazole (standard) in inhibiting C. albicans. In case of anticancer activity none of the molecule exhibited activity better than the standard used (Methotrexate), though they have inhibitory concentration at submicromolar level.

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