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ACS Omega Sep 2020The rising prevalence of multidrug-resistant hospital-acquired infections has increased the need for new antibacterial agents. In this study, a library of 1586...
The rising prevalence of multidrug-resistant hospital-acquired infections has increased the need for new antibacterial agents. In this study, a library of 1586 FDA-approved drugs was screened against , a representative of the complex. Three compounds were found to have previously undiscovered antibacterial properties against : antifungal Miconazole, anthelminthic Dichlorophen, and Bithionol. These three drugs were tested against a wide range of Gram-positive and Gram-negative bacteria and confirmed to have broad-spectrum antibacterial properties. Combinations of these three drugs were also tested against the same bacteria, and two novel combination therapies with synergistic effects were discovered. In the future, antibacterial properties of these three drugs and two combination therapies will be evaluated against pathogenic bacteria using an animal model.
PubMed: 32984715
DOI: 10.1021/acsomega.0c03211 -
Environmental Pollution (Barking, Essex... Aug 2022Dichlorophenol (DCP), a commonly used fungicide and insecticide, is widely found in waters and wastewaters. Herein, the degradation of DCP by Ferrate (Fe(VI)) in...
Dichlorophenol (DCP), a commonly used fungicide and insecticide, is widely found in waters and wastewaters. Herein, the degradation of DCP by Ferrate (Fe(VI)) in different matrices was comprehensively investigated. In pure water, a complete removal of DCP was achieved in 300 s at [Fe(VI)]:[DCP] molar ratio of 2:1. The presence of HA (10 mg L) inhibited DCP degradation to a certain extent. A total of twenty degradation products were identified by HPLC/MS analysis. Based on these products, reaction pathways including the cleavage of C-C bridge bond, hydroxylation, and radical coupling were proposed. These reaction mechanisms were further rationalized by theoretical calculations. The analyses of Wiberg bond orders and transition state indicated that C-C bond was the most vulnerable site for cleavage, and C site was the most likely site for hydroxyl addition. Mulliken atomic spin densities distribution suggested that self-coupling products was easily generated via C-O-C coupling ways. Finally, the feasibility of applying Fe(VI) to degrade DCP (20 μM) in a municipal wastewater effluent and a lake water was evaluated and verified. The findings in this study are of relevance in designing Fe(VI)-based treatment strategy for chlorine-containing persistent pesticides.
Topics: Dichlorophen; Kinetics; Models, Theoretical; Oxidation-Reduction; Oxidative Stress; Phenols; Wastewater; Water; Water Pollutants, Chemical; Water Purification
PubMed: 35525513
DOI: 10.1016/j.envpol.2022.119394 -
Journal of Hazardous Materials Nov 2016As active agents in cleaning and disinfecting products, antimicrobials have been widely spread in the environment and have drawn extensive attention as potential threats...
As active agents in cleaning and disinfecting products, antimicrobials have been widely spread in the environment and have drawn extensive attention as potential threats to the ecological system and human health. In this study, the laccase-catalyzed removal of two emerging antimicrobials, chlorophene (CP) and dichlorophen (DCP), was investigated under simulated environmental conditions. Intrinsic reaction kinetics showed that the removal of CP and DCP followed second-order reaction kinetics, first-order with respect to both the enzyme and the substrate concentration. It was also found that fulvic acid could suppress the transformation of CP and DCP by reversing the oxidation reactions through its action as a scavenger of the free radical intermediates produced from reactions between laccase and the substrates. Several reaction products were identified by a quadrupole time-of-flight mass spectrometer, and detailed reaction pathways were proposed. For both CP and DCP, direct polymerization was the principal pathway, and the coupling patterns were further corroborated based on molecular modeling. The nucleophilic substitution of chlorine by the hydroxyl group was observed, and further oxidation products capable of coupling with each other were also found. Additionally, toxicity evaluation tests using Scenedesmus obliquus confirmed that the toxicity of CP and DCP was effectively eliminated during the reaction processes.
Topics: Anti-Infective Agents; Catalysis; Dichlorophen; Kinetics; Laccase; Scenedesmus; Water Pollutants, Chemical; Water Purification
PubMed: 27262275
DOI: 10.1016/j.jhazmat.2016.05.064 -
Journal of Biomolecular Structure &... Sep 2023To date, no approved drugs are available to treat the Zika virus (ZIKV) infection. Therefore, it is necessary to urgently identify potential drugs against the ZIKV...
To date, no approved drugs are available to treat the Zika virus (ZIKV) infection. Therefore, it is necessary to urgently identify potential drugs against the ZIKV infection. Here, the repurposing of 30 antiparasitic drugs against the NS2B-NS3 protease of the ZIKV has been carried out by using combined docking and molecular dynamics- (MD) simulations. Based on the docking results, 5 drugs, such as Amodiaquine, Primaquine, Paromomycin, Dichlorophene, and Ivermectin were screened for further analysis by MD simulations and free energy calculations. Among these drugs, Amodiaquine and Dichlorophen are found to produce the most stable complexes and possess relative binding free energies of about -44.3 ± 3.7 kcal/mol and -41.1 ± 5.3 kcal/mol respectively. Therefore, they would act as potent small-molecule inhibitors of the ZIKV protease.However, evaluations of biological and safety activities of these drugs against the ZIKV protease are required before their clinical use.Communicated by Ramaswamy H. Sarma.
PubMed: 37747074
DOI: 10.1080/07391102.2023.2255648 -
The Journal of Biological Chemistry May 2020-Acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) (EC 3.1.4.4) catalyzes the final step in the biosynthesis of -acyl-ethanolamides. Reduced NAPE-PLD expression...
-Acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) (EC 3.1.4.4) catalyzes the final step in the biosynthesis of -acyl-ethanolamides. Reduced NAPE-PLD expression and activity may contribute to obesity and inflammation, but a lack of effective NAPE-PLD inhibitors has been a major obstacle to elucidating the role of NAPE-PLD and -acyl-ethanolamide biosynthesis in these processes. The endogenous bile acid lithocholic acid (LCA) inhibits NAPE-PLD activity (with an IC of 68 μm), but LCA is also a highly potent ligand for TGR5 (EC 0.52 μm). Recently, the first selective small-molecule inhibitor of NAPE-PLD, ARN19874, has been reported (having an IC of 34 μm). To identify more potent inhibitors of NAPE-PLD, here we used a quenched fluorescent NAPE analog, PED-A1, as a substrate for recombinant mouse Nape-pld to screen a panel of bile acids and a library of experimental compounds (the Spectrum Collection). Muricholic acids and several other bile acids inhibited Nape-pld with potency similar to that of LCA. We identified 14 potent Nape-pld inhibitors in the Spectrum Collection, with the two most potent (IC = ∼2 μm) being symmetrically substituted dichlorophenes, hexachlorophene and bithionol. Structure-activity relationship assays using additional substituted dichlorophenes identified key moieties needed for Nape-pld inhibition. Both hexachlorophene and bithionol exhibited significant selectivity for Nape-pld compared with nontarget lipase activities such as PLD or serum lipase. Both also effectively inhibited NAPE-PLD activity in cultured HEK293 cells. We conclude that symmetrically substituted dichlorophenes potently inhibit NAPE-PLD in cultured cells and have significant selectivity for NAPE-PLD other tissue-associated lipases.
Topics: Animals; Bacterial Proteins; Bithionol; Dichlorophen; Enzyme Inhibitors; HEK293 Cells; Hexachlorophene; Humans; Mice; Phospholipase D; Quinazolines; Streptomyces; Sulfonamides
PubMed: 32284327
DOI: 10.1074/jbc.RA120.013362 -
Journal of Hazardous Materials May 2022Despite the vital roles of Co nanoparticles catalytic oxidation in the Fenton-like system for eliminating pollutants, contributions of Co phases are typically...
Despite the vital roles of Co nanoparticles catalytic oxidation in the Fenton-like system for eliminating pollutants, contributions of Co phases are typically overlooked. Herein, a biphase Co@C core-shell catalyst was synthesized by the electrochemical co-reduction of CaCO and CoO in molten carbonate. Unlike the traditional pyrolysis method that is performed over 700 °C, the electrolysis was deployed at 450 °C, at which biphase structures, i.e., face-centered cubic (FCC) and hexagonal close-packed (HCP) structures, can be obtained. The biphase Co@C shows excellent catalytic oxidation performance of diethyl phthalate (DEP) with a high turnover frequency value (TOF, 28.14 min) and low catalyst dosage (4 mg L). Furthermore, density functional theory (DFT) calculations confirm that the synergistic catalytic effect of biphase Co@C is the enhancement for the breaking of the peroxide O-O bond and the charge transfer from catalysts to PMS molecule for the activation. Moreover, the results of radicals quenching experiments and electron paramagnetic resonance (EPR) tests confirm that SO, •OH, O, and O co-degrade DEP. Remarkably, 100% removals of three model contaminants, including DEP, sulfamethoxazole (SMX) and 2,4-dichlorophen (2,4-DCP), were achieved, either in pure water or actual river water. This paper provides an electrochemical pathway to leverage the phase of catalysts and thereby mediate their catalytic capability for remediating refractory organic contaminants.
Topics: Catalysis; Cobalt; Oxides; Peroxides; Water Pollutants, Chemical
PubMed: 35065308
DOI: 10.1016/j.jhazmat.2022.128287 -
Environmental Research Jan 2024This study systematically investigated the variable main electrooxidation mechanism of chlorophene (CP) and dichlorophen (DCP) with the change of reaction conditions at...
This study systematically investigated the variable main electrooxidation mechanism of chlorophene (CP) and dichlorophen (DCP) with the change of reaction conditions at TiO anode operated in batch and reactive electrochemical membrane (REM) modes. Significant degradation of CP and DCP was observed, that is, CP exhibited greater removal efficiency in batch mode at 0.5-3.5 mA cm and REM operation (0.5 mA cm) with a permeate flow rate of 0.85 cm min under the same reaction conditions, while DCP exhibited a faster degradation rate with the increase of current density in REM operation. Density functional theory (DFT) simulation and electrochemical performance tests indicated that the electrooxidation efficiency of CP and DCP in batch mode was primarily affected by the mass transfer rates. And the removal efficiency when anodic potentials were less than 1.7 V vs SHE in REM operation was determined by the activation energy for direct electron transfer (DET) reaction, however, the adsorption function of CP and DCP on the TiO anode became a dominant factor in determining the degradation efficiency with the further increase of anodic potential due to the disappeared activation barrier. In addition, the degradation pathways of CP and DCP were proposed according to intermediate products identification and frontier electron densities (FEDs) calculation, the acute toxicity of CP and DCP were also effectively decreased during both batch and REM operations.
Topics: Dichlorophen; Adsorption; Water Pollutants, Chemical; Oxidation-Reduction
PubMed: 37951380
DOI: 10.1016/j.envres.2023.117612 -
Bioconjugate Chemistry Apr 2018Use of pesticides is usually related to overproduction of crops in order to overcome worldwide demand of food and alimentary safety. Nevertheless, pesticides are...
Use of pesticides is usually related to overproduction of crops in order to overcome worldwide demand of food and alimentary safety. Nevertheless, pesticides are environmental persistent molecules, such as the organochlorine pesticides, which are often found in undesired places. In this work, we show that a hybrid nanomaterial (laccase-MSU-F) readily oxidizes the pesticide dichlorophen, reducing its acute genotoxicity and apoptotic effects. In order to predict chronic alterations related to endocrine disruption, we compared the calculated affinity of dichlorophen oxidized subproducts to steroid hormone nuclear receptors (NRs), using molecular simulation methods. We found a reduction in theoretical affinity of subproducts of oxidized dichlorophen for the ligand-binding pocket of NRs (∼5 kcal/mol), likewise of changes in binding modes, that suggests a reduction in binding events (RMSD values < 10 Å).
Topics: Apoptosis; Dichlorophen; Endocrine Disruptors; Enzymes, Immobilized; Kinetics; Laccase; Molecular Docking Simulation; Mutagens; Nanopores; Oxidation-Reduction; Pesticides; Receptors, Cytoplasmic and Nuclear; Structure-Activity Relationship
PubMed: 29337540
DOI: 10.1021/acs.bioconjchem.7b00739 -
Environmental Science and Pollution... Sep 2022Binary composite of zerovalent iron and titanium dioxide (Fe/TiO) was synthesized for the catalytic removal of dichlorophene (DCP) in the presence of peroxymonosulfate...
Binary composite of zerovalent iron and titanium dioxide (Fe/TiO) was synthesized for the catalytic removal of dichlorophene (DCP) in the presence of peroxymonosulfate (PMS). The as-prepared composite (Fe/TiO) exhibits synergistic effect and enhanced properties like improved catalytic activity of catalyst and greater magnetic property for facile recycling of catalyst. The results showed that without addition of PMS at reaction time of 50 min, the percent degradation of DCP by TiO, Fe, and Fe/TiO was just 5%, 11%, and 12%, respectively. However, with the addition of 0.8 mM PMS, at 10 min of reaction time, the catalytic degradation performance of Fe, TiO, and Fe/TiO was significantly improved to 82%, 18%, and 88%, respectively. The as-prepared catalyst was fully characterized to evaluate its structure, chemical states, and morphology. Scanning electron microscopy results showed that in composite TiO causes dispersion of agglomerated iron particles which enhances porosity and surface area of the composites and X-ray diffraction (XRD), energy dispersive X-ray (EDX), and Fourier-transform infrared (FTIR) results revealed successful incorporation of Fe, and oxides of Fe and TiO in the composite. The adsorption-desorption analysis verifies that the surface area of Fe/TiO is significantly larger than bare Fe and TiO Moreover, the surface area, particle size, and crystal size of Fe/TiO was surface area = 85 m g, particle size = 0.35 μm, and crystal size = 0.16 nm as compared to TiO alone (surface area = 22 m g, particle size = 4.25 μm, and crystal size = 25.4 nm) and Fe alone (surface area = 65 m g, particle size = 0.9 μm, and crystal size = 7.87 nm). The as-synthesized material showed excellent degradation performance in synthesized wastewater as well. The degradation products and their toxicities were evaluated and the resulted degradation mechanism was proposed accordingly. The toxicity values decreased in order of DP1 > DP5 > DP2 > DP3 > DP4 and the LC values toward fish for 96-h duration decreased from 0.531 to 67.2. This suggests that the proposed technology is an excellent option for the treatment of antibiotic containing wastewater.
Topics: Animals; Anti-Bacterial Agents; Catalysis; Dichlorophen; Iron; Oxidative Stress; Peroxides; Titanium; Wastewater; Water
PubMed: 35445919
DOI: 10.1007/s11356-022-20174-5 -
Journal of Materials Chemistry. B Oct 2023Conventional nanozyme-based pesticide detection often requires the assistance of acetylcholinesterase. In this work, a CuCeTA nanozyme was successfully designed for the...
Conventional nanozyme-based pesticide detection often requires the assistance of acetylcholinesterase. In this work, a CuCeTA nanozyme was successfully designed for the direct colorimetric detection of glyphosate. Direct detection can effectively avoid the problems caused by cascading with natural enzymes such as acetylcholinesterase. By assembling tannic acid, copper sulfate pentahydrate and cerium(III) nitrate hexahydrate, CuCeTA nanoflowers were prepared. The obtained CuCeTA possessed excellent peroxidase-like activity that could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB in the presence of hydrogen peroxide. Glyphosate could effectively inhibit the peroxidase-like activity of CuCeTA while other pesticides (fenthion, chlorpyrifos, profenofos, phosmet, bromoxynil and dichlorophen) did not show significant inhibitory effects on the catalytic activity of CuCeTA. In this way, CuCeTA could be used for the colorimetric detection of glyphosate with a low detection limit of 0.025 ppm. Combined with a smartphone and imageJ software, a glyphosate test paper was designed with a detection limit of 3.09 ppm. Fourier transform infrared spectroscopy demonstrated that glyphosate and CuCeTA might be bound by coordination, which could affect the catalytic activity of CuCeTA. Our CuCeTA-based nanozyme system exhibited unique selectivity and sensitivity for glyphosate detection and this work may provide a new strategy for rapid and convenient detection of pesticides.
Topics: Peroxidase; Acetylcholinesterase; Colorimetry; Peroxidases; Coloring Agents; Pesticides; Glyphosate
PubMed: 37750214
DOI: 10.1039/d3tb01455j