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Current Protein & Peptide Science 2022Micropollutants comprise organic/mineral substances that cause an undesirable impact on the environment, by affecting life at all scales. In this study, we explored the...
BACKGROUND
Micropollutants comprise organic/mineral substances that cause an undesirable impact on the environment, by affecting life at all scales. In this study, we explored the changes they impart on the global proteome of a soil bacterium Serratia nematodiphila MB307, for two classes of pollutants, i.e., Azo dyes (Methyl orange, Congo red) and a pharmaceutical (Ibuprofen).
METHODS
The 100 μg pollutant supplemented alteration of pure S. nematodiphila MB307 culture after 24 hours of incubation at 37 °C and its control was analyzed using a differential proteomics approach. MaxQuant software with the Perseus package was used for data analysis purposes.
RESULTS
Prominently, ribosomal proteins and chaperones were up or downregulated in the whole cell and membranous fraction.
CONCLUSION
This illustrates dynamic protein production adaptation of bacteria, to cope with stress and cell growth/division trade-off for survival. A collective pattern of survival under stress or pollution resistance could not be decrypted for all classes of pollutants, portraying dissimilar mechanisms of coping with differently structured pollutant moieties.
Topics: Proteome; Ibuprofen; Azo Compounds; Environmental Pollutants
PubMed: 35894467
DOI: 10.2174/1389203723666220727142630 -
Organic Letters Mar 20178-Azacoumarins have emerged as a promising class of compounds but are rarely explored due to challenging access. A novel, general, and practical method is provided for...
8-Azacoumarins have emerged as a promising class of compounds but are rarely explored due to challenging access. A novel, general, and practical method is provided for this class of compounds. The key lactonization step employs trans-acrylic acid attached pyridine N-oxides as the starting material, with acetic anhydride as both the activation agent and the solvent. Multiple transformations were involved in this reaction, including conjugate addition, nucleophilic aromatic substitution, and elimination. These studies provide the basis for access to 8-azacoumarins, enabling future work including the discovery and development of novel coumarin-type drugs, fluorescent probes, photolabile protecting groups, and other active molecules.
Topics: Azo Compounds; Coumarins; Molecular Structure
PubMed: 28186758
DOI: 10.1021/acs.orglett.6b03771 -
Chemical & Pharmaceutical Bulletin 2020Photopharmacology has attracted attention as an approach for the development of novel therapeutics because it allows regulation of the bioactivity of compounds based on...
Photopharmacology has attracted attention as an approach for the development of novel therapeutics because it allows regulation of the bioactivity of compounds based on their conformational change by photo-irradiation. Previously, we have reported several types of selective estrogen receptor (ER) modulators based on diphenylmethane skeleton. To develop novel photopharmacological reagents, we designed and synthesized a set of ER ligands based on azobenzene skeleton, which can switch its conformation following UV irradiation. Our results showed that after UV irradiation, the Z-form of the synthesized compound 9 interacted with ERα, with a K value of 2.5 µM, whereas the E-form of compound 9 did not bind ability to ERα at 10 µM.
Topics: Azo Compounds; Fluorescence Polarization; Humans; Ligands; Molecular Structure; Photochemical Processes; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Stereoisomerism; Structure-Activity Relationship; Ultraviolet Rays
PubMed: 32238658
DOI: 10.1248/cpb.c19-01108 -
International Journal of Molecular... Jun 2020Two series of new hexasubstituted cyclotriphosphazene derivatives were successfully synthesized and characterized. These derivatives are differentiated by two types of...
Two series of new hexasubstituted cyclotriphosphazene derivatives were successfully synthesized and characterized. These derivatives are differentiated by two types of linking units in the molecules such as amide-azo () and azo-azo (). The homologues of the same series contain different terminal substituents such as heptyl, nonyl, decyl, dodecyl, tetradecyl, hydroxyl, carboxyl, chloro, nitro, and amino groups. All the intermediates and final compounds were characterized using Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and Carbon, Hydrogen, and Nitrogen (CHN) elemental analysis. Liquid crystal properties for all compounds were determined using polarized optical microscope (POM). It was found that only intermediates with nitro and alkoxyl terminal chains showed a smectic A phase. All the final compounds with alkoxyl substituents are mesogenic with either smectic A or C phases. However, other intermediates and compounds were found to be non-mesogenic. The study on the fire retardancy of final compounds was determined using limiting oxygen index (LOI) method. The LOI value of pure polyester resin (22.53%) was increased up to 24.71% after treating with 1 wt% of hexachlorocyclotriphosphazene (HCCP). Moreover, all the compounds gave positive results on the LOI values and compound with the nitro terminal substituent showed the highest LOI value of 27.54%.
Topics: Amides; Azo Compounds; Flame Retardants; Liquid Crystals; Microscopy, Polarization; Molecular Structure; Nitriles; Oxygen; Phosphorus Compounds; Spectroscopy, Fourier Transform Infrared
PubMed: 32560033
DOI: 10.3390/ijms21124267 -
Angewandte Chemie (International Ed. in... Jan 2017The p300/CBP-associated factor (PCAF) and related GCN5 bromodomain-containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic...
The p300/CBP-associated factor (PCAF) and related GCN5 bromodomain-containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic tree. Iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine-based L-45 (dubbed L-Moses) as the first potent, selective, and cell-active PCAF bromodomain (Brd) inhibitor. Synthesis from readily available (1R,2S)-(-)-norephedrine furnished L-45 in enantiopure form. L-45 was shown to disrupt PCAF-Brd histone H3.3 interaction in cells using a nanoBRET assay, and a co-crystal structure of L-45 with the homologous Brd PfGCN5 from Plasmodium falciparum rationalizes the high selectivity for PCAF and GCN5 bromodomains. Compound L-45 shows no observable cytotoxicity in peripheral blood mononuclear cells (PBMC), good cell-permeability, and metabolic stability in human and mouse liver microsomes, supporting its potential for in vivo use.
Topics: Azo Compounds; Dose-Response Relationship, Drug; Drug Discovery; Hydralazine; Molecular Probes; Molecular Structure; Structure-Activity Relationship; p300-CBP Transcription Factors
PubMed: 27966810
DOI: 10.1002/anie.201610816 -
Journal of Chromatography. B,... May 2018Lipophilicity as key molecular descriptor of potential biological activity for selected derivatives of azo dyes was determined mathematically, by using relevant software...
Lipophilicity as key molecular descriptor of potential biological activity for selected derivatives of azo dyes was determined mathematically, by using relevant software packages and by reversed-phase thin-layer chromatography (RPTLC) on C18 and cyano modified carriers in mixtures of water/n-propanol and water/acetone. The obtained chromatographic parameters, R and m, of the examined azo dyes were correlated with the standard measure of lipophilicity, log P, important pharmacokinetic predictors and selected toxicity parameters applying linear regression analysis. Thereby, good correlations for each applied system were obtained (average correlation coefficient, r, 0.944, 0.885 and 0.919). Also, the correlations between the studied parameters of azo dyes were examined applying two multivariate methods (Cluster Analysis and Principal Component Analysis). It was shown that the polarity of the substituent, and to a lesser extent its electronic effects has the greatest influence on the studied parameters of the azo dyes derivatives. Multivariate methods pointed out the similarity of the chromatographic retention constant, R, with the parameters of lipophilicity, unlike the chromatographic parameter m, which exhibits better agreement with the toxicity parameters.
Topics: Azo Compounds; Chromatography, Liquid; Hydrophobic and Hydrophilic Interactions; Linear Models; Principal Component Analysis
PubMed: 29604612
DOI: 10.1016/j.jchromb.2018.03.035 -
Angewandte Chemie (International Ed. in... Feb 2022Eg5 is a kinesin motor protein that is responsible for bipolar spindle formation and plays a crucial role during mitosis. Loss of Eg5 function leads to the formation of...
Eg5 is a kinesin motor protein that is responsible for bipolar spindle formation and plays a crucial role during mitosis. Loss of Eg5 function leads to the formation of monopolar spindles, followed by mitotic arrest, and subsequent cell death. Several cell-permeable small molecules have been reported to inhibit Eg5 and some have been evaluated as anticancer agents. We now describe the design, synthesis, and biological evaluation of photoswitchable variants with five different pharmacophores. Our lead compound Azo-EMD is a cell permeable azobenzene that inhibits Eg5 more potently in its light-induced cis form. This activity decreased the velocity of Eg5 in single-molecule assays, promoted formation of monopolar spindles, and led to mitotic arrest in a light dependent way.
Topics: Azo Compounds; Humans; Kinesins; Mitosis; Photochemical Processes; Spindle Apparatus
PubMed: 34958711
DOI: 10.1002/anie.202115846 -
Pakistan Journal of Pharmaceutical... Jan 2024Hydrazones 1-6, azo-pyrazoles 7-9 and azo-pyrimidines 10-15 are compounds that exhibit antibacterial activity. The mode of action and structures of these derivatives...
Hydrazones 1-6, azo-pyrazoles 7-9 and azo-pyrimidines 10-15 are compounds that exhibit antibacterial activity. The mode of action and structures of these derivatives have been previously confirmed as antibacterial. In this investigation, biological screening and molecular docking studies were performed for derivatives 1-15, with compounds 2, 7, 8, 14 and 15 yielding the best energy scores (from -20.7986 to -10.5302 kcal/mol). Drug-likeness and in silico ADME prediction for the most potent derivatives, 2, 7, 8, 14 and 15, were predicted (from 84.46 to 96.85%). The latter compounds showed good recorded physicochemical properties and pharmacokinetics. Compound 8 demonstrated the strongest inhibition, which was similar to the positive control (eflornithine) against Trypanosoma brucei brucei (WT), with an EC of 25.12 and 22.52µM, respectively. Moreover, compound 14 exhibited the best activity against Leishmania mexicana promastigotes and Leishmania major promastigotes (EC =46.85; 40.78µM, respectively).
Topics: Pyrimidines; Molecular Docking Simulation; Trypanosoma brucei brucei; Pyrazoles; Trypanocidal Agents; Leishmania mexicana; Leishmania major; Antiprotozoal Agents; Computer Simulation; Azo Compounds; Structure-Activity Relationship; Parasitic Sensitivity Tests
PubMed: 38747267
DOI: No ID Found -
Journal of the American Chemical Society Sep 2017Biological tissue exhibits an absorbance minimum in the near-infrared between 700 and 900 nm that permits deep penetration of light. Molecules that undergo...
Biological tissue exhibits an absorbance minimum in the near-infrared between 700 and 900 nm that permits deep penetration of light. Molecules that undergo photoisomerization in this bio-optical window are highly desirable as core structures for the development of photopharmaceuticals and as components of chemical-biological tools. We report the systematic design, synthesis, and testing of an azobenzene derivative tailored to undergo single-photon photoswitching with near-infrared light under physiological conditions. A fused dioxane ring and a methoxy substituent were used to place oxygen atoms in all four ortho positions, as well as two meta positions, relative to the azobenzene N═N double bond. This substitution pattern, together with a para pyrrolidine group, raises the pK of the molecule so that it is protonated at physiological pH and absorbs at wavelengths >700 nm. This azobenzene derivative, termed DOM-azo, is stable for months in neutral aqueous solutions, undergoes trans-to-cis photoswitching with 720 nm light, and thermally reverts to the stable trans isomer with a half-life near 1 s.
Topics: Azo Compounds; Hydrogen-Ion Concentration; Infrared Rays; Isomerism; Photochemical Processes; Protons; Pyrrolidines
PubMed: 28885845
DOI: 10.1021/jacs.7b06471 -
The Journal of Physical Chemistry. B Sep 2018Over the past two decades, two-dimensional infrared (2D IR) spectroscopy has evolved from the theoretical underpinnings of nonlinear spectroscopy as a means of... (Review)
Review
Over the past two decades, two-dimensional infrared (2D IR) spectroscopy has evolved from the theoretical underpinnings of nonlinear spectroscopy as a means of investigating detailed molecular structure on an ultrafast time scale. The combined time and spectral resolution over which spectra can be collected on complex molecular systems has led to the precise structural resolution of dynamic species that have previously been impossible to directly observe through traditional methods. The adoption of 2D IR spectroscopy for the study of protein folding and peptide interactions has provided key details of how small changes in conformations can exert major influences on the activities of these complex molecular systems. Traditional 2D IR experiments are limited to molecules under equilibrium conditions, where small motions and fluctuations of these larger molecules often still lead to functionality. Utilizing techniques that allow the rapid initiation of chemical or structural changes in conjunction with 2D IR spectroscopy, i.e., transient 2D IR, a vast dynamic range becomes available to the spectroscopist uncovering structural content far from equilibrium. Furthermore, this allows the observation of reaction pathways of these macromolecules under quasi- and nonequilibrium conditions.
Topics: Azo Compounds; Disulfides; Heterocyclic Compounds, 1-Ring; Peptides; Protein Conformation; Protein Folding; Spectrophotometry, Infrared; Temperature
PubMed: 30040900
DOI: 10.1021/acs.jpcb.8b05063