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Bioorganic & Medicinal Chemistry Dec 2004To improve the biological activities of chrysin (CR), we synthesize Diethyl Chysin-7-yl phosphate (CPE: C(19)H(19)O(7)P) and tetraethyl bis-phosphoric ester of chrysin...
To improve the biological activities of chrysin (CR), we synthesize Diethyl Chysin-7-yl phosphate (CPE: C(19)H(19)O(7)P) and tetraethyl bis-phosphoric ester of chrysin (CP: C(23)H(28)O(10)P(2)) through a simplified Atheron-Todd reaction. The interactions of the CR and CPE with lysozyme were explored by electrospray ionization mass spectrometry (ESI) and fluorescence spectrometry method. Experimental results indicate that CPE could form the noncovalent compound with lysozyme, while the interaction of the CR with lysozyme was not detected. In addition, whether and how the compounds CPE and CP affect proliferation and apoptosis in human cervical cancer Hela cells were investigated. Moreover, the effects of CPE and CP in Hela cells were compared with that of the nonmodified CR compound. The Hela cells were co-cultured with CR, CP, and CPE as experimental groups, respectively, and corresponding control groups treated without CR, CP, and CPE. The proliferation and apoptosis were detected using MTT assay, HCl denatured-methyl green-pyronin staining, PCNA immunohistochemistry and TUNEL techniques. The cell growth IC(50), relative absorbance (RA), proliferating index (PI), PCNA-IR (immunoreactivity IR) integration value (IV), and apoptosis index (AI) were calculated and their correlation was analyzed in each group. The results show that all CR, CP, and CPE could inhibit proliferation and induce apoptosis in Hela cells. Moreover, the effects of CP and CPE were more potent than that of CR. The CP and CPE were proved to be a kind of stronger apoptosis inducers than nonphosphated CR. There was a negative correlation between proliferation and apoptosis. In conclusion, the CR, CP, and CPE could effectively inhibit growth by down-regulated expression of PCNA, and induce apoptosis in Hela cells. The efficiency of the modified CP and CPE preceded nonmodified CR compounds. The CP and CPE may be a new potential anti-cancer drug for therapy of human cervical carcinoma.
Topics: Antineoplastic Agents; Apoptosis; Cell Proliferation; Flavonoids; HeLa Cells; Humans; In Situ Nick-End Labeling; Muramidase; Organophosphates; Proliferating Cell Nuclear Antigen; Protein Binding; Structure-Activity Relationship
PubMed: 15519155
DOI: 10.1016/j.bmc.2004.09.013 -
Chemosphere Dec 2019In 2015, nine laboratories from Belgium, USA, Canada, China, and Australia participated in an interlaboratory exercise to quantify metabolites of organophosphate ester...
In 2015, nine laboratories from Belgium, USA, Canada, China, and Australia participated in an interlaboratory exercise to quantify metabolites of organophosphate ester (OPE) contaminants in pooled human urine. Pooled human urine available as SRM 3673 (Organic contaminants in non-smokers' urine) was obtained from the U.S. National Institute of Standards and Technology and was analyzed for its content of OPE metabolites. Each participating laboratory received 10 mL sample and used its own validated method and standards to report the concentrations of the OPE metabolites of its choice. Four OPE metabolites were consistently measured by most laboratories and they were the following diesters: bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), bis(2-chloroethyl) phosphate (BCEP), and bis(1-chloro-2-propyl) phosphate (BCIPP). Concentrations of other OPE metabolites in SRM 3673 were also reported but are only considered as informative values since they were measured by three laboratories at most. All laboratories used liquid chromatography with tandem mass spectrometry (LC-MS/MS) with or without solid-phase extraction (SPE). This is the first study to report indicative values for OPE metabolites in a human urine Standard Reference Material. It is expected that these indicative values obtained for these four metabolites will be used as quality control to ensure compatibility of results in biomonitoring studies and by other researchers who validate their own methods for the quantification of OPE metabolites in human urine.
Topics: Australia; Belgium; Biological Monitoring; Biphenyl Compounds; Canada; China; Chromatography, Liquid; Flame Retardants; Humans; Organophosphates; Organophosphonates; Organophosphorus Compounds; Phosphoric Acids; Research Design; Solid Phase Extraction; Tandem Mass Spectrometry; United States
PubMed: 31326757
DOI: 10.1016/j.chemosphere.2019.124348 -
Chemical Communications (Cambridge,... Mar 2018Phosphate ester hydrolysis is fundamental to many life processes, and has been the topic of substantial experimental and computational research effort. However, even the... (Review)
Review
Phosphate ester hydrolysis is fundamental to many life processes, and has been the topic of substantial experimental and computational research effort. However, even the simplest of phosphate esters can be hydrolyzed through multiple possible pathways that can be difficult to distinguish between, either experimentally, or computationally. Therefore, the mechanisms of both the enzymatic and non-enzymatic reactions have been historically controversial. In the present contribution, we highlight a number of technical issues involved in reliably modeling these computationally challenging reactions, as well as proposing potential solutions. We also showcase examples of our own work in this area, discussing both the non-enzymatic reaction in aqueous solution, as well as insights obtained from the computational modeling of organophosphate hydrolysis and catalytic promiscuity amongst enzymes that catalyze phosphoryl transfer.
Topics: Alkaline Phosphatase; Biocatalysis; Computer Simulation; Hydrolysis; Models, Molecular; Molecular Structure; Organophosphates; Phosphates; Quantum Theory
PubMed: 29412205
DOI: 10.1039/c7cc09504j -
International Journal of Environmental... Jan 2022Organophosphate (OP) pesticides are associated with numerous adverse health outcomes. Pesticide use data are available for California from the Pesticide Use Report...
Organophosphate (OP) pesticides are associated with numerous adverse health outcomes. Pesticide use data are available for California from the Pesticide Use Report (PUR), but household- and individual-level exposure factors have not been fully characterized to support its refinement as an exposure assessment tool. Unique exposure pathways, such as proximity to agricultural operations and direct occupational contact, further complicate pesticide exposure assessment among agricultural communities. We sought to identify influencing factors of pesticide exposure to support future exposure assessment and epidemiological studies. Household dust samples were collected from 28 homes in four California agricultural communities during January and June 2019 and were analyzed for the presence of OPs. Factors influencing household OPs were identified by a data-driven model via best subsets regression. Key factors that impacted dust OP levels included household cooling strategies, secondary occupational exposure to pesticides, and geographic location by community. Although PUR data demonstrate seasonal trends in pesticide application, this study did not identify season as an important factor, suggesting OP persistence in the home. These results will help refine pesticide exposure assessment for future studies and highlight important gaps in the literature, such as our understanding of pesticide degradation in an indoor environment.
Topics: Agriculture; Dust; Environmental Exposure; Housing; Humans; Organophosphates; Pesticides
PubMed: 35055689
DOI: 10.3390/ijerph19020862 -
Journal of Hazardous Materials Aug 2022Most investigations on organophosphate esters (OPEs) are conducted predominantly in a separate biological or abiotic medium, and few joint analyses have been performed...
Most investigations on organophosphate esters (OPEs) are conducted predominantly in a separate biological or abiotic medium, and few joint analyses have been performed in the mariculture ecosystem based on yearly sampling. Herein, we investigated the occurrence, load estimation, phase distribution, source diagnostics, and risks of 20 OPEs in seawater, sediment, and aquaculture organisms from a typical mariculture area in China. The total of these OPEs (∑) ranged within 3.97-1068 ng/L, 0.39-65.5 ng/g (dw), and 4.09-16.3 ng/g (ww) in seawater, sediment and organisms, respectively. Chlorinated OPEs were the predominant congeners detected in seawater, whereas alkyl-OPEs were the leading contributors in sediment and biological samples. Seasonal variations of ∑ in seawater were more distinct than those in sedimentary environments. Load estimation indicated that approximately 70% of the OPEs in the study area existed in the water bodies. Source identification performed using the U.S. EPA positive matrix factorization indicated that polyurethane foam/plastics and hydraulic oil made the greatest contributions in seawater, whereas chemical production was the predominant source in sediment. Indices of ecological and health risks of OPEs were lower than their risk threshold, indicating that the OPEs detected in this study posed a low risk to the aquatic environment and human health.
Topics: China; Ecosystem; Environmental Monitoring; Esters; Flame Retardants; Humans; Organophosphates; Risk Assessment; Water Pollutants, Chemical
PubMed: 35739741
DOI: 10.1016/j.jhazmat.2022.129219 -
Environmental Pollution (Barking, Essex... Apr 2024As a major alternative to the brominated flame retardants, the production and use of organophosphorus flame retardants (OPFRs) are increasing. And tris... (Review)
Review
As a major alternative to the brominated flame retardants, the production and use of organophosphorus flame retardants (OPFRs) are increasing. And tris (1,3-dichloro-2-propyl) phosphate (TDCPP), one of the most widely used OPFRs, is now commonly found in a variety of products, such as building materials, furniture, bedding, electronic equipment, and baby products. TDCPP does not readily degrade in the water and tends to accumulate continuously in the environment. It has been detected in indoor dust, air, water, soil, and human samples. Considered as an emerging environmental pollutant, increasing studies have demonstrated its adverse effects on environmental organisms and human beings, with the nerve system identified as a sensitive target organ. This paper systematically summarized the progress of TDCPP application and its current exposure in the environment, with a focus on its neurotoxicity. In particular, we highlighted that TDCPP can be neurotoxic (including neurodevelopmentally toxic) to humans and animals, primarily through oxidative stress, neuroinflammation, mitochondrial damage, and epigenetic regulation. Additionally, this paper provided an outlook for further studies on neurotoxicity of TDCPP, as well as offered scientific evidence and clues for rational application of TDCPP in daily life and the prevention and control of its environmental impact in the future.
Topics: Animals; Humans; Phosphates; Organophosphates; Organophosphorus Compounds; Flame Retardants; Epigenesis, Genetic; Water
PubMed: 38369091
DOI: 10.1016/j.envpol.2024.123569 -
Chemical Research in Toxicology Dec 2021Triphenyl phosphate (TPhP) is a broad-spectrum organophosphate compound widely used as an additive in several products to prevent ignition. However, its utilization...
Triphenyl phosphate (TPhP) is a broad-spectrum organophosphate compound widely used as an additive in several products to prevent ignition. However, its utilization produces a hazardous impact on various organisms. So far, very few studies have investigated the acute toxicity of TPhP at environmentally relevant concentrations in nontarget aquatic species. This study aimed to assess whether the short-term exposure of TPhP (4, 20, and 100 μg L) affects the oxidative stress, antioxidant activity, biomolecule metabolism, DNA stability, chromosomal integrity, apoptosis, and pathological changes in various organs of fingerlings. The results illustrated that the reactive oxygen species (ROS) production and lipid peroxidation (LPO) rates were significantly higher in tissues (brain, liver, and kidney) of TPhP-treated groups. Interestingly, superoxide dismutase (SOD) and catalase (CAT) activities were remarkably decreased in tissues following TPhP exposure. The levels of protein, glucose, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in various tissues were also found to be significantly altered in TPhP-exposed fish fingerlings. These significant alterations in the antioxidant system and biochemical profile induced genotoxic responses such as DNA and chromosomal damage in the fish fingerlings. Furthermore, the incidence of the observed genotoxic responses was also found to be dose-dependent. Likewise, the apoptotic responses were also significantly altered following TPhP acute exposure in fingerlings. The subsequent effects on oxidative stress, antioxidant inhibition, dysregulated biomolecule metabolism, and genotoxicity might be the possible reason for the observed pathological changes in various tissues of . Taken together, the present findings showed that the toxicity of TPhP is principally associated with exposure concentrations. Therefore, this study illustrates the toxicity risks of TPhP to vertebrate organisms at real-world concentrations.
Topics: Animals; Antioxidants; Apoptosis; Brain; Carps; DNA Damage; Dose-Response Relationship, Drug; Kidney; Lipid Peroxidation; Molecular Structure; Organophosphates; Oxidative Stress; Reactive Oxygen Species
PubMed: 34847329
DOI: 10.1021/acs.chemrestox.1c00281 -
Journal of Colloid and Interface Science Oct 2014Uni-lamellar and multi-lamellar vesicles were prepared by the enantiomers of a biological molecule, L-lysine or D-lysine, with a double-tail weak monoacid,...
Uni-lamellar and multi-lamellar vesicles were prepared by the enantiomers of a biological molecule, L-lysine or D-lysine, with a double-tail weak monoacid, di-(2-ethylhexyl) phosphoric acid (abbreviated as DEHPA), in water. With the addition of DEHPA to lysine aqueous solutions, ion-pairs are formed through the acid-base reaction between the lysine cations and DEHP(-) anions. The self-assembled vesicles were proved to be driven by the hydrogen bonding between the side-chain amino groups in lysine molecules and the polar groups of DEHP(-) species. The combination of DEHPA and lysine through electrostatic interactions and hydrogen bonding reduces the cross-sectional area of the hydrophilic groups, improving the surface activity and inducing a microstructural transition from primitive aggregates to micelles, and to vesicles in solution. Due to the chirality of the lysine molecules, the aggregates exhibited diverse chiral properties along with the microstructural transitions.
Topics: Lysine; Organophosphates
PubMed: 25016167
DOI: 10.1016/j.jcis.2014.05.069 -
ACS Sensors Jan 2020Environmental hazards typically are encountered in the gaseous phase; however, selective sensing modalities for identifying and quantitating compounds of interest in an...
Environmental hazards typically are encountered in the gaseous phase; however, selective sensing modalities for identifying and quantitating compounds of interest in an inexpensive, pseudo-real-time format are severely lacking. Here, we present a novel proof-of-concept that combines an Air2Liquid sampler in conjunction with an oil-in-water microfluidic assay for detection of organophosphates. We believe this proof-of-concept will enable development of a new platform technology for semivolatile detection that we have demonstrated to detect 50 pmoles (2 ppb) of neurotoxic organophosphates.
Topics: Biosensing Techniques; Gases; Organophosphates
PubMed: 31833351
DOI: 10.1021/acssensors.9b01624 -
Mini Reviews in Medicinal Chemistry May 2004This review depicts in vitro and in vivo results obtained with nucleotide prodrugs (pronucleotides) bearing S-acyl-2-thioethyl (SATE) groups as esterase-labile phosphate... (Review)
Review
This review depicts in vitro and in vivo results obtained with nucleotide prodrugs (pronucleotides) bearing S-acyl-2-thioethyl (SATE) groups as esterase-labile phosphate protections. New developments are illustrated by the design of mononucleoside mixed phosphoester derivatives leading to the selective intracellular delivery of the corresponding 5'-mononucleotide through two different enzyme-mediated activation steps.
Topics: Animals; Antiviral Agents; Cell Division; HIV-1; Hepatitis B virus; Humans; Kinetics; Nucleotides; Organophosphates; Prodrugs; Structure-Activity Relationship; Time Factors
PubMed: 15134542
DOI: 10.2174/1389557043404007