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Water Research Jul 2021Nitrite (NO)-sensitized photolysis plays an important role in the attenuation of effluent-derived trace organic contaminants (e.g., anilines, phenolic compounds, etc.)...
Nitrite (NO)-sensitized photolysis plays an important role in the attenuation of effluent-derived trace organic contaminants (e.g., anilines, phenolic compounds, etc.) in surface waters. However, the kinetics, mechanisms, and influencing factors of photolysis of many emerging contaminants sensitized by NO still remain largely unknown. Herein, we report that NO-sensitized photolysis of the antimicrobial agents parachlormetaxylenol (PCMX) and chlorophene (CP) in aqueous solution under ultraviolet 365 nm (UV) radiation. A nonlinear increase in photolysis rate constants of PCMX and CP was observed with increasing NO concentration. Radical quenching studies and kinetic modeling revealed that hydroxyl radical (HO•) and nitrogen dioxide radicals (NO) contributed dominantly to the removal of PCMX and CP. Solid phase extraction (SPE) combined with high resolution-mass spectrometry (HR-MS) analysis identified a series of intermediate products including hydroxylated, nitrated, nitrosated, and dimerized derivatives. Experiments with isotopically labelled nitrite (NO) showed that the nitro- and nitroso-substituents of intermediate products were derived from the nitrite nitrogen. Based on the identified products and theoretical computations, the mechanisms and pathways of NO-sensitized photolysis of PCMX and CP are elucidated. Deoxygenation partially inhibited the formation of 4-chloro-3,5-dimethyl-2-nitrophenol (nitro-PCMX) while the presence of HO• scavenger such as isopropanol (i-PrOH) suppressed the further transformation of nitro-PCMX. The presence of Mississippi River natural organic matter (MRNOM) inhibited the removal of PCMX and CP, likely due to light screening and radical quenching. However, appreciable degradation of PCMX and CP was still observed in wastewater and wetland water matrices. Results of this study shed some light on the transformation and fate of PCMX and CP in NO-rich wastewater effluents or effluent-impacted surface waters under solar radiation.
Topics: Anti-Infective Agents; Dichlorophen; Mississippi; Nitrites; Photolysis; Water; Water Pollutants, Chemical
PubMed: 34087514
DOI: 10.1016/j.watres.2021.117275 -
Water Research Apr 2021Mineral-humic complexes, known as mineral-associated organic matter (MAOM), are ubiquitous in natural waters. However, the interaction between organic pollutants and...
Mineral-humic complexes, known as mineral-associated organic matter (MAOM), are ubiquitous in natural waters. However, the interaction between organic pollutants and MAOM remains elusive, which may affect their degradation process. In this study, photochemical transformation of chlorophene (CP) in the presence of MAOM, prepared by coating aluminum hydroxide with humic acid (HA-HAO), was investigated. Our results showed that the degradation of CP was significantly enhanced in the presence of HA-HAO, and the degradation rate constant was ~5 times as that with HA only. It was because the adsorption of CP to HA-HAO particles was greatly enhanced, and concentration of reactive oxygen species (ROS) was increased on HA-HAO surfaces, which further promoted the reactions between CP and ROS. The quenching experiments combined with EPR technology confirmed that superoxide anion (O) was the primary reactive radical on CP photodegradation. More importantly, the degradation of CP with HA-HAO followed a hydroxylation process, rather than the oligomerization reaction with HA only. Spectroscopic analysis provided direct evidence for the formation of hydrogen bonding between CP phenolic hydroxyl group and surface oxygen of HAO, which would suppress the reactivity of phenolic hydroxyl group, consequently the ortho- and meta-positions of CP became more facile for the hydroxylation reaction. This study shows the importance of MAOM in altering the photochemical behavior and transformation pathway of organic contaminants.
Topics: Aluminum Hydroxide; Dichlorophen; Humic Substances; Photolysis; Water Pollutants, Chemical
PubMed: 33582491
DOI: 10.1016/j.watres.2021.116904 -
Biosensors Feb 2021Chlorophene is an important antimicrobial agent present in disinfectant products which has been related to health and environmental effects, and its detection has been...
Chlorophene is an important antimicrobial agent present in disinfectant products which has been related to health and environmental effects, and its detection has been limited to chromatographic techniques. Thus, there is a lack of research that attempts to develop new analytical tools, such as biosensors, that address the detection of this emerging pollutant. Therefore, a new biosensor for the direct detection of chlorophene in real water is presented, based on surface plasmon resonance (SPR) and using a laccase enzyme as a recognition element. The biosensor chip was obtained by covalent immobilization of the laccase on a gold-coated surface through carbodiimide esters. The analytical parameters accomplished resulted in a limit of detection and quantification of 0.33 mg/L and 1.10 mg/L, respectively, fulfilling the concentrations that have already been detected in environmental samples. During the natural river's measurements, no significant matrix effects were observed, obtaining a recovery percentage of 109.21% ± 7.08, which suggested that the method was suitable for the fast and straightforward analysis of this contaminant. Finally, the SPR measurements were validated with an HPLC method, which demonstrated no significant difference in terms of precision and accuracy, leading to the conclusion that the biosensor reflects its potential as an alternative analytical tool for the monitoring of chlorophene in aquatic environments.
Topics: Anti-Infective Agents; Biosensing Techniques; Carbodiimides; Dichlorophen; Gold; Limit of Detection; Surface Plasmon Resonance
PubMed: 33572259
DOI: 10.3390/bios11020043 -
Environmental Health Perspectives Oct 2020Endocrine-disrupting chemicals can interfere with hormonal homeostasis and have adverse effects for both humans and the environment. Their identification is increasingly...
BACKGROUND
Endocrine-disrupting chemicals can interfere with hormonal homeostasis and have adverse effects for both humans and the environment. Their identification is increasingly difficult due to lack of adequate toxicological tests. This difficulty is particularly problematic for cosmetic ingredients, because testing is now banned completely in the European Union.
OBJECTIVES
The aim was to identify candidate preservatives as endocrine disruptors by methods and to confirm endocrine receptors' activities through nuclear receptors .
METHODS
We screened preservatives listed in Annex V in the European Union Regulation on cosmetic products to predict their binding to nuclear receptors using the Endocrine Disruptome and VirtualToxLab™ version 5.8 tools. Five candidate preservatives were further evaluated for androgen receptor (AR), estrogen receptor (), glucocorticoid receptor (GR), and thyroid receptor (TR) agonist and antagonist activities in cell-based luciferase reporter assays in AR-EcoScreen, , MDA-kb2, and GH3.TRE-Luc cell lines. Additionally, assays to test for false positives were used (nonspecific luciferase gene induction and luciferase inhibition).
RESULTS
Triclocarban had agonist activity on AR and at and antagonist activity on GR at and TR at . Triclosan showed antagonist effects on AR, , GR at and TR at , and bromochlorophene at (AR and TR) and at ( and GR). AR antagonist activity of chlorophene was observed [inhibitory concentration at 50% (IC) ], as for its substantial agonist at and TR antagonist activity at . Climbazole showed AR antagonist (), agonist at , and TR antagonist activity at .
DISCUSSION
These data support the concerns of regulatory authorities about the endocrine-disrupting potential of preservatives. These data also define the need to further determine their effects on the endocrine system and the need to reassess the risks they pose to human health and the environment. https://doi.org/10.1289/EHP6596.
Topics: Androgen Receptor Antagonists; Carbanilides; Cell Line; Computer Simulation; Dichlorophen; Endocrine Disruptors; Genes, Reporter; Humans; Imidazoles; Receptors, Androgen; Receptors, Estrogen; Receptors, Glucocorticoid; Triclosan
PubMed: 33064576
DOI: 10.1289/EHP6596 -
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 -
ACS Omega Sep 2020Of the numerous infectious diseases afflicting humans, anthrax disease, caused by , poses a major threat in its virulence and lack of effective treatment. The currently...
Of the numerous infectious diseases afflicting humans, anthrax disease, caused by , poses a major threat in its virulence and lack of effective treatment. The currently lacking standards of care, as well as the lengthy drug approval process, demonstrate the pressing demand for treatment for infections. The present study screened 1586 clinically approved drugs in an attempt to identify repurposable compounds against , a relative strain that shares many physical and genetic characteristics with . Our study yielded five drugs that successfully inhibited growth: dichlorophen, oxiconazole, suloctidil, bithionol, and hexestrol. These drugs exhibited varying levels of efficacy in broad-spectrum experiments against several Gram-positive and Gram-negative bacterial strains, with hexestrol showing the greatest inhibition across all tested strains. Through tests for the efficacy of each drug on , bithionol was the single most potent compound on both solid and liquid media and exhibited even greater eradication of in combination with suloctidil on solid agar. This multifaceted study of approved drugs demonstrates the potential to repurpose these drugs as treatments for anthrax disease in a time-efficient manner to address a global health need.
PubMed: 32905429
DOI: 10.1021/acsomega.0c03207 -
Brazilian Journal of Microbiology :... Dec 2020With the high-frequency use or abuse of antifungal drugs, the crisis of drug-resistant fungi continues to increase worldwide; in particular, the infection of...
With the high-frequency use or abuse of antifungal drugs, the crisis of drug-resistant fungi continues to increase worldwide; in particular, the infection of drug-resistant Candida albicans brings the great challenge to the clinical treatment. Therefore, to decelerate the spread of this resistance, it is extremely urgent to facilitate the new antifungal targets with novel drugs. Phosphopantetheinyl transferases PPTases (Ppt2 in Candida albicans) had been identified in bacterium and fungi and mammals, effects as a vital enzyme in the metabolism of organisms in C. albicans. Ppt2 transfers the phosphopantetheinyl group of coenzyme A to the acyl carrier protein Acp1 in mitochondria for the synthesis of lipoic acid that is essential for fungal respiration, so making Ppt2 an ideal target for antifungal drugs. In this study, 110 FDA-approved drugs were utilized to investigate the Ppt2 inhibition against drug-resistant Candida albicans by the improved fluorescence polarization experiments, which have enough druggability and structural variety under the novel strategy of drug repurposing. Thereinto, eight agents revealed the favourable Ppt2 inhibitory activities. Further, broth microdilution assay of incubating C. albicans with these eight drugs showed that pterostilbene, procyanidine, dichlorophen and tea polyphenol had the superior MIC values. In summary, these findings provide more valuable insight into the treatment of drug-resistant C. albicans.
Topics: Antifungal Agents; Candida albicans; Drug Repositioning; Drug Resistance, Fungal; Enzyme Inhibitors; Fungal Proteins; Microbial Sensitivity Tests; Transferases (Other Substituted Phosphate Groups)
PubMed: 32557281
DOI: 10.1007/s42770-020-00318-w -
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 -
Parasitology Nov 2019Alveolar echinococcosis is a neglected parasitic zoonosis caused by the metacestode Echinococcus multilocularis, which grows as a malignant tumour-like infection in the...
Alveolar echinococcosis is a neglected parasitic zoonosis caused by the metacestode Echinococcus multilocularis, which grows as a malignant tumour-like infection in the liver of humans. Albendazole (ABZ) is the antiparasitic drug of choice for the treatment of the disease. However, its effectiveness is low, due to its poor absorption from the gastro-intestinal tract. It is also parasitostatic and in some cases produces side-effects. Therefore, an alternative to the treatment of this severe human disease is necessary. In this context, the repositioning of drugs combined with nanotechnology to improve the bioavailability of drugs emerges as a useful, fast and inexpensive tool for the treatment of neglected diseases. The in vitro and in vivo efficacy of dichlorophen (DCP), an antiparasitic agent for intestinal parasites, and silica nanoparticles modified with DCP (NP-DCP) was evaluated against E. multilocularis larval stage. Both formulations showed a time and dose-dependent in vitro effect against protoscoleces. The NP-DCP had a greater in vitro efficacy than the drug alone or ABZ. In vivo studies demonstrated that the NP-DCP (4 mg kg-1) had similar efficacy to ABZ (25 mg kg-1) and greater activity than the free DCP. Therefore, the repurposing of DCP combined with silica nanoparticles could be an alternative for the treatment of echinococcosis.
Topics: Animals; Antiparasitic Agents; Dichlorophen; Drug Repositioning; Drug Therapy, Combination; Echinococcosis; Echinococcus multilocularis; Female; Life Cycle Stages; Mice; Nanoparticles; Nanotechnology; Silicon Dioxide
PubMed: 31397256
DOI: 10.1017/S0031182019001057 -
Journal of Colloid and Interface Science Oct 2019Mesoporous NH-MIL-125(Ti)@BiMoO core-shell heterojunctions with surface defects were fabricated through a facile solvothermal method. The mesoporous core-shell structure...
Surface-defect-rich mesoporous NH-MIL-125 (Ti)@BiMoO core-shell heterojunction with improved charge separation and enhanced visible-light-driven photocatalytic performance.
Mesoporous NH-MIL-125(Ti)@BiMoO core-shell heterojunctions with surface defects were fabricated through a facile solvothermal method. The mesoporous core-shell structure with a large relative surface area of 87.7 m g and narrow pore size of 8.2 nm extends the photoresponse to the range of visible light due to the narrow band gap of ∼1.89 eV. The visible-light-driven photocatalytic degradation efficiency of highly toxic dichlorophen and trichlorophenol were 93.28 and 92.19%, respectively, and the corresponding rate constants were approximately 8 and 17 times higher than the rates achieved by pristine NH-MIL-125(Ti). The photocatalytic oxygen production rate was increased to 171.3 µmol g. Recycling for several cycles indicates high stability, which is favorable for practical applications. The excellent photocatalytic performance can be ascribed to the formation of the core-shell heterojunctions and to the surface defects that favor charge separation and visible light absorption; the mesoporous structure offers an adequate number of surface active sites and mass transfer. This novel mesoporous core-shell photocatalyst will have potential applications in the environment, and this strategy offers a new insight into fabrication of other high-performance core-shell structure photocatalysts.
PubMed: 31306944
DOI: 10.1016/j.jcis.2019.07.021