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Critical Reviews in Toxicology Nov 2020A cancer weight of evidence (WOE) analysis based on updated toxicokinetics, genotoxicity, and carcinogenicity data for 1,3-dichloropropene was peer reviewed by a panel... (Review)
Review
Peer review of a cancer weight of evidence assessment based on updated toxicokinetics, genotoxicity, and carcinogenicity data for 1,3-dichloropropene using a blinded, virtual panel of experts.
A cancer weight of evidence (WOE) analysis based on updated toxicokinetics, genotoxicity, and carcinogenicity data for 1,3-dichloropropene was peer reviewed by a panel of experts. Historically, 1,3-dichloropropene has been classified in the U.S. as "likely to be carcinogenic to humans" via oral and inhalation exposure routes based upon the results of rodent cancer bioassays conducted in the 1980s. Contemporary studies led the authors of the WOE analysis to conclude that the currently manufactured form of 1,3-dichloropropene is not mutagenic and not carcinogenic below certain doses, pointing to a threshold-based approach for cancer risk assessment. SciPinion conducted a peer review of the WOE analysis using methods for assembling and managing blinded expert panels that maximize expertise while minimizing potential selection/participation bias. The process was implemented through a web-based application that poses a series of questions soliciting the experts' scientific opinions and observations about specific topics. The goal of the peer review was to have experts provide conclusions about the WOE for carcinogenicity classification of 1,3-dichloropropene, identify potential data gaps, and evaluate the validity of a threshold-based risk assessment for 1,3-dichloropropene. Based on a robust peer review of the current scientific information, a cancer WOE classification of "not likely to be carcinogenic to humans" is best supported for 1,3-dichloropropene. This conclusion is reached with a high degree of consensus (consensus score = 0.92) across expert panel members.
Topics: Allyl Compounds; Animals; Carcinogenesis; Carcinogens; DNA Damage; Humans; Hydrocarbons, Chlorinated; Mutagenicity Tests; Mutagens; Neoplasms; Peer Review; Pesticides; Risk Assessment; Toxicokinetics
PubMed: 33528305
DOI: 10.1080/10408444.2020.1854680 -
In Vivo (Athens, Greece) 2015Resveratrol is a polyphenol with efficient anti-oxidative and anti-inflammatory activity. To clarify the molecular mechanism responsible for its anti-inflammatory...
The Radical Scavenging Activity and Cytotoxicity of Resveratrol, Orcinol and 4-Allylphenol and their Inhibitory Effects on Cox-2 Gene Expression and Nf-κb Activation in RAW264.7 Cells Stimulated with Porphyromonas gingivalis-fimbriae.
BACKGROUND/AIM
Resveratrol is a polyphenol with efficient anti-oxidative and anti-inflammatory activity. To clarify the molecular mechanism responsible for its anti-inflammatory action, we investigated the radical scavenging activity, cytotoxicity and anti-inflammatory activity of resveratrol and its related compounds, orcinol and 4-allylphenol.
MATERIALS AND METHODS
The radical scavenging activities of these compounds were determined by the DPPH (2,2'-diphenyl-1-picrylhydrazyl) assay and their cytotoxicities against RAW264.7 cells were determined using a cell-counting kit (CCK-8). The inhibitory effects of these compounds on cyclooxygenase-2 (Cox2) expression in RAW264.7 cells stimulated with Porphyromonas gingivalis (Pg) fimbriae were also determined using real-time polymerase chain reaction and western blot analysis, while inhibition of the fimbria-stimulated activation of nuclear factor-kappa B (Nf-κb) was evaluated using western blot analysis and enzyme-linked immunosorbent assay-like microwell colorimetric transcription factor activity assay, respectively. The quantum chemical parameters were calculated on the basis of the density function theory (DFT) BLYP/6-31G*.
RESULTS
DPPH radical scavenging activity declined in the order resveratrol > orcinol > 4-allylphenol. The cytotoxicity of the compounds was in the order 4-allylphenol > resveratrol > orcinol. The inhibitory effect on Pg fimbria-stimulated Cox2 expression and Nf-κb activation was enhanced by resveratrol-alone. Resveratrol showed high electronegativity (χ) and softness (σ) values, as determined by quantum chemical calculations.
CONCLUSION
Resveratrol exerts potent anti-inflammatory activity in RAW264.7 cells stimulated with Pg-fimbriae and may be applicable as a therapeutic agent for inflammatory periodontal disease as a manifestation of systemic disease.
Topics: Allyl Compounds; Animals; Biphenyl Compounds; Cell Line; Drug Evaluation, Preclinical; Fimbriae, Bacterial; Free Radical Scavengers; Free Radicals; Mice; NF-kappa B; Phenols; Picrates; Porphyromonas gingivalis; Resorcinols; Resveratrol; Stilbenes
PubMed: 25977379
DOI: No ID Found -
Oncotarget Dec 2016The improvement of solubility and/or dissolution rate of poorly soluble natural compounds is an ideal strategy to make them optimal candidates as new potential drugs....
The improvement of solubility and/or dissolution rate of poorly soluble natural compounds is an ideal strategy to make them optimal candidates as new potential drugs. Accordingly, the allyl sulfur compounds and omega-3 fatty acids are natural hydrophobic compounds that exhibit two important combined properties: cardiovascular protection and antitumor activity. Here, we have synthesized and characterized a novel formulation of diallyl disulfide (DADS) and α-linolenic acid (ALA) as protein-nanoemulsions (BAD-NEs), using ultrasounds. BAD-NEs are stable over time at room temperature and show antioxidant and radical scavenging property. These NEs are also optimal H2S slow-release donors and show a significant anti-proliferative effect on different human cancer cell lines: MCF-7 breast cancer and HuT 78 T-cell lymphoma cells. BAD-NEs are able to regulate the ERK1/2 pathway, inducing apoptosis and cell cycle arrest at the G0/G1 phase. We have also investigated their effect on cell proliferation of human adult stem/progenitor cells. Interestingly, BAD-NEs are able to improve the Lin- Sca1+ human cardiac progenitor cells (hCPC) proliferation. This stem cell growth stimulation is combined with the expression and activation of proteins involved in tissue-repair, such as P-AKT, α-sma and connexin 43. Altogether, our results suggest that these antioxidant nanoemulsions might have potential application in selective cancer therapy and for promoting the muscle tissue repair.
Topics: Allyl Compounds; Antineoplastic Agents; Apoptosis; Cardiotonic Agents; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Disulfides; Emulsions; Female; Humans; Hydrogen Sulfide; MCF-7 Cells; Microscopy, Electron, Scanning; Myocardium; Nanostructures; Neoplasms; Stem Cells
PubMed: 27741519
DOI: 10.18632/oncotarget.12609 -
Angewandte Chemie (International Ed. in... Sep 2018The first catalytic, broadly applicable, efficient, γ-, diastereo-, and enantioselective method for addition of O-substituted allyl-B(pin) compounds to...
The first catalytic, broadly applicable, efficient, γ-, diastereo-, and enantioselective method for addition of O-substituted allyl-B(pin) compounds to phosphinoylimines (MEM=methoxyethoxymethyl, pin=pinacolato) is presented. The identity of the most effective catalyst and the optimal protecting group for the organoboron reagent were determined by consideration of the steric and electronic requirements at different stages of the catalytic cycle, namely, the generation of the chiral allylboronate, the subsequent 1,3-borotropic shift, and the addition step. Aryl-, heteroaryl-, alkenyl- and alkyl-substituted vicinal phosphinoylamido MEM-ethers were thus accessed in 57-92 % yield, 89:11 to >98:2 γ:α selectivity, 76:24-97:3 diastereomeric ratio, and 90:10-99:1 enantiomeric ratio. The method is scalable, and the phosphinoyl and MEM groups may be removed selectively or simultaneously. Utility is highlighted by enantioselective synthesis of an NK-1 receptor antagonist.
Topics: Allyl Compounds; Ammonium Compounds; Boron Compounds; Catalysis; Imines; Models, Molecular; Phosphorylation; Stereoisomerism
PubMed: 29969173
DOI: 10.1002/anie.201805811 -
Nature Communications Sep 2021Spirocycles play an important role in drug discovery and development. The direct, catalytic, and enantioselective synthesis of spirocycles from readily available...
Spirocycles play an important role in drug discovery and development. The direct, catalytic, and enantioselective synthesis of spirocycles from readily available starting materials and in an atom economic manner remains a highly sought-after task in organic synthesis. Herein, an enantioselective Pd-hydride-catalyzed cycloaddition method for the synthesis of spirocyclic compounds directly from two classes of commonly available starting materials, 1,3-enynes and cyclic carbon-hydrogen (C-H) bonds, is reported. The reactions employ a chiral Pd/WingPhos catalyst to both suppress the formation of bis-allenyl by-products and control the stereoselectivity. 1,3-Enynes are used as dielectrophilic four-carbon units in the cycloaddition reactions, which also enables an enyne substrate-directed enantioselectivity switch with good levels of stereocontrol. The present spirocycle synthesis tolerates a broad range of functional groups of 1,3-enyne substrates, including alcohols, esters, nitriles, halides, and olefins. A variety of diverse cyclic nucleophiles, including pharmaceutically important heterocycles and carbocycles, can be flexibly incorporated with spiro scaffolds.
Topics: Allyl Compounds; Catalysis; Cycloaddition Reaction; Molecular Structure; Palladium; Stereoisomerism
PubMed: 34580311
DOI: 10.1038/s41467-021-25981-x -
Molecules (Basel, Switzerland) Feb 2023DATS (diallyl trisulfide), an anti-oxidant and cytotoxic chemical derived from the plant garlic, has been found to have potential therapeutic activity against...
DATS (diallyl trisulfide), an anti-oxidant and cytotoxic chemical derived from the plant garlic, has been found to have potential therapeutic activity against triple-negative breast cancer (TNBC). Its hydrophobicity, short half-life, lack of target selectivity, and limited bioavailability at the tumor site limit its efficacy in treating TNBC. Overexpression of the Folate receptor on the surface of TNBC is a well-known target receptor for overcoming off-targeting, and lipid nanoparticles solve the limitations of limited bioavailability and short half-life. In order to overcome these constraints, we developed folic acid (FA)-conjugated DATS-SLNs in this research. The design of experiment (DoE) method was employed to optimize the FA-DATS-SLNs' nanoformulation, which resulted in a particle size of 168.2 ± 3.78 nm and a DATS entrapment of 71.91 ± 6.27%. The similarity index between MCF-7 and MDA-MB-231 cell lines demonstrates that FA-DATS-SLNs are more therapeutically efficacious in the treatment of aggravating TNBC. Higher cellular internalization and efficient Bcl2 protein downregulation support the hypothesis that functionalization of the FA on the surface of DATS-SLNs improves anticancer efficacy when compared with DATS and DATS-SLNs. FA-functionalized DATS-SLNs have demonstrated to be a promising therapeutic strategy for TNBC management.
Topics: Humans; Triple Negative Breast Neoplasms; Cell Line, Tumor; Apoptosis; Sulfides; Allyl Compounds; Nanoparticles
PubMed: 36771058
DOI: 10.3390/molecules28031393 -
Journal of the American Chemical Society Oct 2017We report a Rh-catalyzed hydroamination of 1,3-dienes to generate homoallylic amines. Our work showcases the first case of anti-Markovnikov selectivity in the...
We report a Rh-catalyzed hydroamination of 1,3-dienes to generate homoallylic amines. Our work showcases the first case of anti-Markovnikov selectivity in the intermolecular coupling of amines and 1,3-dienes. By tuning the ligand properties and Brønsted acid additive, we find that a combination of rac-BINAP and mandelic acid is critical for achieving anti-Markovnikov selectivity.
Topics: Alkenes; Allyl Compounds; Amination; Amines; Catalysis; Ligands; Mandelic Acids; Naphthalenes; Rhodium
PubMed: 28953374
DOI: 10.1021/jacs.7b09188 -
Journal of the American Chemical Society Sep 2014Biological systems have long recognized the importance of macromolecular diversity and have evolved efficient processes for the rapid synthesis of sequence-defined...
Biological systems have long recognized the importance of macromolecular diversity and have evolved efficient processes for the rapid synthesis of sequence-defined biopolymers. However, achieving sequence control via synthetic methods has proven to be a difficult challenge. Herein we describe efforts to circumvent this difficulty via the use of orthogonal allyl acrylamide building blocks and a liquid-phase fluorous support for the de novo design and synthesis of sequence-specific polymers. We demonstrate proof-of-concept via synthesis and characterization of two sequence-isomeric 10-mer polymers. (1)H NMR and LCMS were used to confirm their chemical structure while tandem MS was used to confirm sequence identity. Further validation of this methodology was provided via the successful synthesis of a sequence-specific 16-mer polymer incorporating nine different monomers. This strategy thus shows promise as an efficient approach for the assembly of sequence-specific functional polymers.
Topics: Acrylamide; Allyl Compounds; Halogenation; Models, Molecular; Polymers; Sulfhydryl Compounds
PubMed: 25204618
DOI: 10.1021/ja507262t -
IET Nanobiotechnology Aug 2018Despite the unique properties, application of garlic essential oil (GEO) is too limited in food and drugs, due to its low water solubility, very high volatility and...
Despite the unique properties, application of garlic essential oil (GEO) is too limited in food and drugs, due to its low water solubility, very high volatility and unpleasant odour. In this work, a nanoemulsion containing GEO was formulated to cover and protect the volatile compounds of GEO. The encapsulation efficiency of formulated nanoemulsions was measured by gas chromatography and obtained encapsulation efficiency ranged from 91 to 77% for nanoemulsions containing 5-25% GEO, respectively. The 2,2-diphenyl-1-picrylhydrazyl method for antioxidant activity measurement showed that free radical scavenging capacity of nanoemulsions intensified during storage time. The electrical conductivity of the samples was constant over storage time while linearly increased by raising the temperature. Thermogravimetric analysis was used to determine the thermal resistance of nanoemulsions and their ingredients. Interestingly, microbial tests cleared that the control nanoemulsion with a particle size below 100 nm (nanoemulsion without GEO) also showed antimicrobial activity. Disk diffusion method showed that pure GEO and also formulated nanoemulsions had a stronger effect against Gram-positive bacterium () than Gram-negative bacterium ().
Topics: Allyl Compounds; Anti-Infective Agents; Antioxidants; Biphenyl Compounds; Electric Conductivity; Emulsions; Escherichia coli; Microbial Sensitivity Tests; Nanostructures; Particle Size; Picrates; Staphylococcus aureus; Sulfides; Water
PubMed: 30095427
DOI: 10.1049/iet-nbt.2017.0104 -
Bioorganic Chemistry Jun 2020In this study, we described the microbial catalyzed allylic oxidation by Bacillus megaterium CGMCC 1.1741 of three Δ-pentacyclic triterpenes, erythrodiol (1), uvaol...
In this study, we described the microbial catalyzed allylic oxidation by Bacillus megaterium CGMCC 1.1741 of three Δ-pentacyclic triterpenes, erythrodiol (1), uvaol (2), hederagenin (3) and of four steroids including Δ-steroids, diosgenin (4), pennogenin (5), 25(R,S)-ruscogenin (6) and Δ-steroid, diosgenone (7). As a result, fourteen metabolites were generated with allyl hydroxyl moiety. Ten (1a-c, 2a, 2c, 3a, 5a-b, and 6a-b) of them were new natural products and their structures were determined on the basis of 1D/2D NMR and HR-MS data. Biocatalytic allylic oxidation by B. megaterium CGMCC 1.1741 is thus a potential non-toxic and efficient alternative method toward metal-mediated oxidation procedures in the synthesis of natural products and medicines.
Topics: Allyl Compounds; Bacillus megaterium; Hydroxylation; Molecular Conformation; Oxidation-Reduction; Steroids; Triterpenes
PubMed: 32315895
DOI: 10.1016/j.bioorg.2020.103826