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International Journal of Nanomedicine 2019It is well known that the grafted multiwalled carbon nanotubes (MWCNTs) have antibacterial activity and lower cytotoxicity. Moreover, pyrazole derivatives have a broad...
INTRODUCTION
It is well known that the grafted multiwalled carbon nanotubes (MWCNTs) have antibacterial activity and lower cytotoxicity. Moreover, pyrazole derivatives have a broad spectrum of biological activity due to their fertile template for many medicinal drugs. On view of these findings we report herein the hybridization between MWCNTs and some pyrazole derivatives as antibacterial agents.
MATERIALS AND METHODS
Pyrazole and pyrazolone derivatives were grafted onto the surface of carboxylated MWCNTs via the reaction of carboxylated MWCNTs and the diazonium salts of pyrazoles and pyrazolones using mixed acid treatment. The insertion of the pyrazole and pyrazolone moieties was characterized by Fourier transform infrared (FTIR) spectroscopy, energy dispersion spectroscopy, transmission electron microscopy, X-ray diffraction and thermogravimetric (TGA).
RESULTS
The results indicate that pyrazole and pyrazolone moieties successfully attached on carboxylated MWCNTs surface. The neat pyrazole and pyrazolone derivatives and their corresponding carbon nanotubes were tested against , and bacteria, and fungi. The results showed that the grafted carbon nanotubes of pyrazole and pyrazolone derivatives have better antimicrobial activity than the neat pyrazole and pyrazolone derivatives. The molecular docking studies were performed on the most potent antimicrobial compounds to investigate the existence of the interactions between the most active inhibitors and Farnesyl pyrophosphate synthase (FPPS).
CONCLUSION
The surface of the carboxylated MWCNTs was successfully grafted with some pyrazole derivatives. The antibacterial activity was investigated for the newly synthesized compounds and indicated that the grafted MWCNTs have good antibacterial activity toward some pathogenic types of bacteria.
Topics: Anti-Bacterial Agents; Bacteria; Catalytic Domain; Fungi; Ligands; Microbial Sensitivity Tests; Molecular Docking Simulation; Nanotubes, Carbon; Pyrazoles; Spectroscopy, Fourier Transform Infrared; Thermogravimetry; X-Ray Diffraction
PubMed: 31686804
DOI: 10.2147/IJN.S182699 -
Chembiochem : a European Journal of... Jan 2020Ultraviolent crosslinking is a key experimental step in the numerous protocols that have been developed for capturing and dissecting RNA-protein interactions in living...
Ultraviolent crosslinking is a key experimental step in the numerous protocols that have been developed for capturing and dissecting RNA-protein interactions in living cells. UV crosslinking covalently stalls dynamic interactions between RNAs and the directly contacting RNA-binding proteins and enables stringent denaturing downstream purification conditions needed for the enrichment and biochemical analysis of RNA-protein complexes. Despite its popularity, conventional 254 nm UV crosslinking possesses a set of intrinsic drawbacks, with the low photochemical efficiency being the central caveat. Here we show that genetically encoded photoreactive unnatural amino acids bearing a dialkyl diazirine photoreactive group can address this problem. Using the human iron regulatory protein 1 (IRP1) as a model RNA-binding protein, we show that the photoreactive amino acids can be introduced into the protein without diminishing its RNA-binding properties. A sevenfold increase in the crosslinking efficiency compared to conventional 254 nm UV crosslinking was achieved using the diazirine-based unnatural amino acid DiAzKs. This finding opens an avenue for new applications of the unnatural amino acids in studying RNA-protein interactions.
Topics: Cross-Linking Reagents; Diazomethane; Humans; Molecular Structure; RNA; RNA-Binding Proteins; Ultraviolet Rays
PubMed: 31658407
DOI: 10.1002/cbic.201900559 -
The Journal of Organic Chemistry Nov 2019It is well established that the -nitrosoamide derived from peracetylated derivatives of -acetyl neuraminic acid on treatment with a mixture of sodium isopropoxide and...
Use of Phenols as Nucleophiles in the Zbiral Oxidative Deamination of -Acetyl Neuraminic Acid: Isolation and Characterization of Tricyclic 3-Keto-2-deoxy-nonulosonic Acid (KDN) Derivatives via an Intermediate Vinyl Diazonium Ion.
It is well established that the -nitrosoamide derived from peracetylated derivatives of -acetyl neuraminic acid on treatment with a mixture of sodium isopropoxide and trifluoroethanol, followed by the addition of acetic acid, gives an oxidative deamination product, in which the AcN(NO)-C5 bond is replaced with a AcO-C5 bond with the retention of configuration, affording a practical synthesis of 2-keto-3-deoxy-d-glycero-d-galactononulosonic acid (KDN) derivatives. Application of other strong acids, including hydrogen fluoride, thioacetic acid, trifluoromethanesulfonic acid, and hydrogen azide, functions similarly to afford KDN derivatives functionalized at the 5-position. We describe our attempts to extend the range of useful nucleophiles employed in this oxidative deamination process to include phenols and thiophenols, resulting in the discovery of a new branch of the general reaction and the formation of a series of products resulting from substitution of the 5-acetamido group and of the 4-acetoxy group from neuraminic acid. A mechanistic rationale for the formation of these products is advanced according to which, in the absence of acids of p ≤ 8, the intermediate diazonium ion resulting from the elimination of acetic acid and nitrogen from the nitrosoacetamide undergoes elimination of acetic acid from the 4-position to afford a highly electrophilic alkenediazonium ion. Reversible conjugate addition of the nucleophile to the 4-position then initiates the reaction cascade leading to the ultimate products.
Topics: Deamination; Diazonium Compounds; Ions; Molecular Conformation; N-Acetylneuraminic Acid; Oxidation-Reduction; Phenols; Sugar Acids
PubMed: 31608634
DOI: 10.1021/acs.joc.9b02279 -
Molecules (Basel, Switzerland) Oct 2019A simple general synthesis of 1-aryl-6-azaisocytosine-5-carbonitriles is described. This method is based on coupling diazonium salts with cyanoacetylcyanamide and then...
A simple general synthesis of 1-aryl-6-azaisocytosine-5-carbonitriles is described. This method is based on coupling diazonium salts with cyanoacetylcyanamide and then cyclization of the formed 2-arylhydrazono-2-cyanoacetylcyanamides . The 6-azaisocytosines were studied with respect to tautomeric equilibrium and the transformation of functional groups, and used in the synthesis of the condensed heterocyclic compounds: Purine isosteric imidazo[2,1-]-[1,2,4]triazine and the 1,2,4-triazino[2,3-]quinazolines -.
Topics: Cyclization; Cytosine; Molecular Structure; Pyrimidines; Triazines
PubMed: 31581428
DOI: 10.3390/molecules24193558 -
Molecules (Basel, Switzerland) Sep 2019The Pd-catalyzed intramolecular carbene C-H insertion of α-diazo-α-(methoxycarbonyl)acetamides to prepare oxindoles as well as β-lactams was studied. In order to...
Site Selectivity in Pd-Catalyzed Reactions of α-Diazo-α-(methoxycarbonyl)acetamides: Effects of Catalysts and Substrate Substitution in the Synthesis of Oxindoles and β-Lactams.
The Pd-catalyzed intramolecular carbene C-H insertion of α-diazo-α-(methoxycarbonyl)acetamides to prepare oxindoles as well as β-lactams was studied. In order to identify what factors influence the selectivity of the processes, we explored how the reactions are affected by the catalyst type, using two oxidation states of Pd and a variety of ligands. It was found that, in the synthesis of oxindoles, ((IMes)Pd(NQ)) can be used as an alternative to Pd(dba) to catalyze the carbene Csp-H insertion, although it was less versatile. On the other hand, it was demonstrated that the Csp-H insertion leading to β-lactams can be effectively promoted by both Pd(0) and Pd(II) catalysts, the latter being most efficient. Insight into the reaction mechanisms involved in these transformations was provided by DFT calculations.
Topics: Acetamides; Catalysis; Diazonium Compounds; Models, Molecular; Molecular Structure; Oxindoles; Palladium; beta-Lactams
PubMed: 31575030
DOI: 10.3390/molecules24193551 -
Mediators of Inflammation 2019Macrophages have variable functional phenotypes, high diversity, and plasticity and are involved in the pathogenesis of sepsis-induced liver injury. Alteration of...
Macrophages have variable functional phenotypes, high diversity, and plasticity and are involved in the pathogenesis of sepsis-induced liver injury. Alteration of macrophage polarization through activated (M1) macrophage to alternatively activated (M2) macrophage has emerged as a potential therapeutic strategy. This study was designed to explore the effect of a benzenediamine analog FC-99 on macrophage polarization in vitro and lipopolysaccharide- (LPS-) induced liver injury followed by the underlying mechanisms. For in vitro experiments, FC-99 inhibited M1-related macrophage factors and promoted M2-related markers induced by IL-4 in the mouse macrophage cell line RAW264.7. Moreover, FC-99-induced macrophages polarized to M2 phenotype which could be repressed by a PPAR- inhibitor but not STAT6 siRNA knockdown, indicating FC-99-induced M2 macrophage polarization through PPAR- rather than STAT6 signal. In LPS-induced septic mice, FC-99 pretreated mice displayed lower expression of M1 markers together with the increased M2 marker CD206 and improvement of liver injury. These findings illustrated that FC-99 could promote M2 macrophage polarization via PPAR- signaling and seemed to be a potential therapeutic candidate for inflammatory liver injury.
Topics: Animals; Blotting, Western; Chemical and Drug Induced Liver Injury; Diazonium Compounds; Flow Cytometry; Fluorescent Antibody Technique; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred BALB C; RAW 264.7 Cells; RNA, Small Interfering; Signal Transduction
PubMed: 31467487
DOI: 10.1155/2019/7823069 -
The Plant Cell Oct 2019
Topics: Basic Helix-Loop-Helix Transcription Factors; Cyclopentanes; Diazonium Compounds; Marchantia; Oxylipins; Pyridines
PubMed: 31416824
DOI: 10.1105/tpc.19.00600 -
Nature Microbiology Dec 2019Bacterial autotrophs often rely on CO concentrating mechanisms (CCMs) to assimilate carbon. Although many CCM proteins have been identified, a systematic screen of the...
Bacterial autotrophs often rely on CO concentrating mechanisms (CCMs) to assimilate carbon. Although many CCM proteins have been identified, a systematic screen of the components of CCMs is lacking. Here, we performed a genome-wide barcoded transposon screen to identify essential and CCM-related genes in the γ-proteobacterium Halothiobacillus neapolitanus. Screening revealed that the CCM comprises at least 17 and probably no more than 25 genes, most of which are encoded in 3 operons. Two of these operons (DAB1 and DAB2) contain a two-gene locus that encodes a domain of unknown function (Pfam: PF10070) and a putative cation transporter (Pfam: PF00361). Physiological and biochemical assays demonstrated that these proteins-which we name DabA and DabB, for DABs accumulate bicarbonate-assemble into a heterodimeric complex, which contains a putative β-carbonic anhydrase-like active site and functions as an energy-coupled inorganic carbon (C) pump. Interestingly, DAB operons are found in a diverse range of bacteria and archaea. We demonstrate that functional DABs are present in the human pathogens Bacillus anthracis and Vibrio cholerae. On the basis of these results, we propose that DABs constitute a class of energized C pumps and play a critical role in the metabolism of C throughout prokaryotic phyla.
Topics: Archaea; Bacillus anthracis; Bacteria; Bacterial Proteins; Carbon; Carbon Dioxide; Carbonic Anhydrases; Carrier Proteins; DNA Transposable Elements; Diazonium Compounds; Genes, Bacterial; Genes, Essential; Halothiobacillus; Mutagenesis; Operon; Prokaryotic Cells; Sulfanilic Acids; Vibrio cholerae
PubMed: 31406332
DOI: 10.1038/s41564-019-0520-8 -
Molecules (Basel, Switzerland) Jul 2019The intramolecular C-H insertions of carbenes derived from 2-diazo-2-sulfamoylacetamides were studied. 2-Diazo-2-sulfamoylacetamides were first prepared from...
The intramolecular C-H insertions of carbenes derived from 2-diazo-2-sulfamoylacetamides were studied. 2-Diazo-2-sulfamoylacetamides were first prepared from chloroacetyl chloride and secondary amines through acylation followed by sequential treatments with sodium sulfite, phosphorus oxychloride, secondary amines, and 4-nitrobenzenesulfonyl azide. The results indicate that: (1) 2-diazo--dimethyl-2-(-diphenylsulfamoyl)acetamide can take the formal aromatic 1,5-C-H insertion in its -phenylsulfonamide moiety to afford the corresponding 1,3-dihydrobenzo[]isothiazole-3-carboxamide 2,2-dioxide derivative; (2) no aliphatic C-H insertions occur for 2-diazo-2-(-dialkylsulfamoyl)acetamides; and (3) for 2-diazo--phenyl-2-(-phenylsulfamoyl)acetamides, the formal aromatic 1,5-C-H insertion in the -phenylacetamide moiety is favorable to afford the corresponding 3-sulfamoylindolin-2-one derivatives as sole or major products. The intramolecular competitive aromatic 1,5-C-H insertion reactions of 2-diazo-2-sulfamoylacetamides with aryl groups on both amide and sulfonamide groups reveal that the -aryl substituents on acetamide are more active than those on sulfonamide. The chemoselectivity is controlled by electronic effect of the aryl group.
Topics: Acetamides; Carbon; Catalysis; Diazonium Compounds; Hydrogen; Methane; Sulfonamides
PubMed: 31330952
DOI: 10.3390/molecules24142628 -
Anti-infective Agents Apr 2019Antibiotics play an important role in the treatment of infections to the hu-mans and at the same time, irrational, frequent prescription of higher antibiotics, change in...
BACKGROUND
Antibiotics play an important role in the treatment of infections to the hu-mans and at the same time, irrational, frequent prescription of higher antibiotics, change in gene com-position of microorganisms are all the reasons behind the development and introduction of new anti-biotics against different microorganisms.
OBJECTIVE
In this project, an attempt has been made to synthesize some derivatives of diazenyl con-taining phenyl styryl ketones and also their in vitro screening was conducted against Mycobacterium tuberculosis, Escherichia coli, Klebsiella pneumonia, Bacillus subtilis, Staphylococcus aureus, As-pergillus niger and Candida albicans.
METHODS
Ten molecules were synthesized which are diazenyl containing chalcones. 4-aminoacetophenone was diazotised and piperidine was coupled with the formed diazonium chloride. Further, the acetoxy group underwent Claisen-Schmidt condensation with differently substituted al-dehydes to form the final compounds- the chalcones. The proposed chemical structures were con-firmed by different spectroscopic techniques like FTIR, 1H NMR and Mass spectroscopy. TLC was used to know that the reactants were exhausted and the formation of the product occurred. Sharp melting point of the compounds concludes the purity.
RESULTS
The MIC of the compounds 3CP, 3DP, 3EP and 3GP is 20 times the MIC of the standard fluconazole drug against Aspergillus niger. The compound 3GP is as equipotent as the standard drug Pyrazinamide with MIC of 3.12 µg/ml against Mycobacterium tuberculosis.
CONCLUSION
The results are quite promising which on further studies may lead to drug molecules against different microorganisms. Especially, 3EP can be considered as a broad spectrum agent due to its potent activity against different microorganisms like Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia and Candida albicans.
PubMed: 31328083
DOI: 10.2174/2211352516666180927111546