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Chemico-biological Interactions Sep 2023As part of a systematic review of the non-cancer and cancer hazards of propylene dichloride (PDC), with a focus on potential carcinogenicity in workers following... (Review)
Review
As part of a systematic review of the non-cancer and cancer hazards of propylene dichloride (PDC), with a focus on potential carcinogenicity in workers following inhalation exposures, we determined that a mode of action (MOA)-centric framing of cancer effects was warranted. In our MOA analysis, we systematically reviewed the available mechanistic evidence for PDC-induced carcinogenesis, and we mapped biologically plausible MOA pathways and key events (KEs), as guided by the International Programme on Chemical Safety (IPCS)-MOA framework. For the identified pathways and KEs, biological concordance, essentiality of KEs, concordance of empirical observations among KEs, consistency, and analogy were evaluated. The results of this analysis indicate that multiple biologically plausible pathways may contribute to the cancer MOA for PDC, but that the relevant pathways vary by exposure route and level, tissue type, and species; further, more than one pathway may occur concurrently at high exposure levels. While several important data gaps exist, evidence from in vitro mechanistic studies, in vivo experimental animal studies, and ex vivo human tumor tissue analyses indicates that the predominant MOA pathway likely involves saturation of cytochrome p450 2E1 (CYP2E1)-glutathione (GSH) detoxification (molecular initiating event; MIE), accumulation of CYP2E1-oxidative metabolites, cytotoxicity, chronic tissue damage and inflammation, and ultimately tumor formation. Tumors may occur through several subsets of inflammatory KEs, including inflammation-induced aberrant expression of activation-induced cytidine deaminase (AID), which causes DNA strand breaks and mutations and can lead to tumors with a characteristic mutational signature found in occupational cholangiocarcinoma. Dose concordance analysis showed that low-dose mutagenicity (from any pathway) is not a driving MOA, and that prevention of target tissue damage and inflammation (associated with saturation of CYP2E1-GSH detoxification) is expected to also prevent the cascade of processes responsible for tumor formation.
Topics: Propane; Humans; DNA Damage; Carcinogens; Inflammation; Cytochrome P-450 CYP2E1; Metabolic Networks and Pathways; Carcinogenesis; Animals; Cholangiocarcinoma; Glutathione
PubMed: 36754223
DOI: 10.1016/j.cbi.2023.110382 -
Langmuir : the ACS Journal of Surfaces... Jan 2023Small organic molecules have been shown to produce sufficient power densities allowing them to be environmentally friendly renewable fuel sources and an important part...
Small organic molecules have been shown to produce sufficient power densities allowing them to be environmentally friendly renewable fuel sources and an important part of fuel cell research. Affiliated experimental work found propylene glycol, as a source of renewable fuel, produces viable power densities when utilized with an alkaline-acid fuel cell and a Pd(111) catalyst. There is limited theoretical work on propylene glycol's energy reaction pathway. Thus, the first step in understanding how propylene glycol reacts with the Pd(111) slab is understanding its adsorption. In this paper, we present the investigation of adsorption potential energies (APE) of propylene glycol stereoisomers ()-propane-1,2-diol (1,2PGS), ()-propane-1,2-diol (1,2PGR), and propane-1,3-diol (1,3PG) on Pd(111). The isomers are systematically scanned through different configurations to analyze the preferred stable orientation and positional motifs. Density functional theory (DFT) is used to optimize the molecular geometries and surface relaxations. The most stable configuration of the 1,2PG stereoisomers resulted in an APE of -0.97 eV. The most stable configuration of the 1,3PG resulted in an APE of -1.19 eV. Both the 1,2PG(S/R) and 1,3PG isomers favor a motif in which at least one hydroxyl oxygen atom interacts with the surface of the Pd(111) catalyst. The 1,2PG carbon backbone prefers to have the center carbon positioned away from the slab, while the 1,3PG prefers to have the center carbon positioned closer to the slab. The most stable 1,3PG differs from other reported 1,3PG and 1,2PG relaxed configurations in that both of the hydroxyl oxygen atoms interact with the Pd(111) surface. These results show more favorable APEs than previously reported calculations. This paper will discuss in detail the differences between the hydroxyl group motifs and their role in affecting adsorption.
Topics: Adsorption; Carbon; Oxygen; Palladium; Propane; Propylene Glycol; Stereoisomerism
PubMed: 36583559
DOI: 10.1021/acs.langmuir.2c02281 -
Journal of Water and Health Jun 2021The goals of this research are to evaluate which chemical contaminations were detected in Brazil's drinking water reported in papers published from 2012 to 2019, to...
The goals of this research are to evaluate which chemical contaminations were detected in Brazil's drinking water reported in papers published from 2012 to 2019, to propose guideline values for emerging contaminants and assess which are the priority parameters from a health risk perspective. The methodology used was a systematic review. The chemical contaminants quantified were evaluated according to Brazilian drinking-water standards, and Guideline Values were proposed for emerging pollutants using conservative endpoints from NOAEL and LOAEL available in literature. From 1351 articles evaluated, 15 reached the research goal. Seventy-seven parameters were quantified in Brazilian drinking water from underground, surface and rainwater sources. Soil composition, mining, sewage and agricultural activities were the main sources for the seven classes framed: pesticides, metals, organic, endocrine disruptors, drugs, personal care products and illicit drugs. Twenty-two parameters are listed in the current Brazilian drinking water quality standard and 54 are not. Water was not considered appropriate to drink due to cadmium, aluminum, iron, nickel, mercury, atrazine, propionaldehyde, beryllium, acetone and 17 α-ethinyl estradiol (carcinogenic). Measures to reduce chemical contamination in drinking water need to be taken such as the expansion of sewage treatment and upgrading to tertiary treatment, and controlling and reducing the application of pesticides.
Topics: Brazil; Drinking Water; Environmental Monitoring; Mercury; Water Pollutants, Chemical; Water Quality
PubMed: 34152292
DOI: 10.2166/wh.2021.264 -
Phytochemistry Reviews : Proceedings of... 2022Medicinal plants are one of the most important sources of antiviral agents and lead compounds. Lignans are a large class of natural compounds comprising two phenyl... (Review)
Review
Medicinal plants are one of the most important sources of antiviral agents and lead compounds. Lignans are a large class of natural compounds comprising two phenyl propane units. Many of them have demonstrated biological activities, and some of them have even been developed as therapeutic drugs. In this review, 630 lignans, including those obtained from medicinal plants and their chemical derivatives, were systematically reviewed for their antiviral activity and mechanism of action. The compounds discussed herein were published in articles between 1998 and 2020. The articles were identified using both database searches (e.g., Web of Science, Pub Med and Scifinder) using key words such as: antiviral activity, antiviral effects, lignans, HBV, HCV, HIV, HPV, HSV, JEV, SARS-CoV, RSV and influenza A virus, and directed searches of scholarly publisher's websites including ACS, Elsevier, Springer, Thieme, and Wiley. The compounds were classified on their structural characteristics as 1) arylnaphthalene lignans, 2) aryltetralin lignans, 3) dibenzylbutyrolactone lignans, 4) dibenzylbutane lignans, 5) tetrahydrofuranoid and tetrahydrofurofuranoid lignans, 6) benzofuran lignans, 7) neolignans, 8) dibenzocyclooctadiene lignans and homolignans, and 9) norlignans and other lignoids. Details on isolation and antiviral activities of the most active compounds within each class of lignan are discussed in detail, as are studies of synthetic lignans that provide structure-activity relationship information.
PubMed: 34093097
DOI: 10.1007/s11101-021-09758-0 -
Frontiers in Pharmacology 2020Pain is considered an unpleasant sensory and emotional experience, being considered as one of the most important causes of human suffering. Computational chemistry...
INTRODUCTION
Pain is considered an unpleasant sensory and emotional experience, being considered as one of the most important causes of human suffering. Computational chemistry associated with bioinformatics has stood out in the process of developing new drugs, through natural products, to manage this condition.
OBJECTIVE
To analyze, through literature data, recent molecular coupling studies on the antinociceptive activity of essential oils and monoterpenes.
DATA SOURCE
Systematic search of the literature considering the years of publications between 2005 and December 2019, in the electronic databases PubMed and .
ELIGIBILITY CRITERIA
Were considered as criteria of 1) Biological activity: non-clinical effects of an OE and/or monoterpenes on antinociceptive activity based on animal models and analysis, 2) studies with plant material: chemically characterized essential oils and/or their constituents isolated, 3) clinical and non-clinical studies with analysis to assess antinociceptive activity, 4) articles published in English. Exclusion criteria were literature review, report or case series, meta-analysis, theses, dissertations, and book chapter.
RESULTS
Of 16,006 articles, 16 articles fulfilled all the criteria. All selected studies were non-clinical. The most prominent plant families used were Asteraceae, Euphorbiaceae, Verbenaceae, Lamiaceae, and Lauraceae. Among the phytochemicals studied were α-Terpineol, 3-(5-substituted-1,3,4-oxadiazol-2-yl)-N'-[2-oxo-1,2-dihydro-3H-indol-3-ylidene] propane hydrazide, β-cyclodextrin complexed with citronellal, (-)-α-bisabolol, β-cyclodextrin complexed with farnesol, and p-Cymene. The softwares used for docking studies were Molegro Virtual Docker, SybylX, Vlife MDS, AutoDock Vina, Hex Protein Docking, and AutoDock 4.2 in PyRx 0.9. The molecular targets/complexes used were Nitric Oxide Synthase, COX-2, GluR2-S1S2, TRPV1, β-CD complex, CaV, CaV, CaV, and CaV, 5-HT receptor, delta receptor, kappa receptor, and MU (μ) receptor, alpha adrenergic, opioid, and serotonergic receptors, muscarinic receptors and GABA opioid and serotonin receptors, 5-HT and M receptors. Many of the covered studies used molecular coupling to investigate the mechanism of action of various compounds, as well as molecular dynamics to investigate the stability of protein-ligand complexes.
CONCLUSIONS
The studies revealed that through the advancement of more robust computational techniques that complement the experimental studies, they may allow some notes on the identification of a new candidate molecule for therapeutic use.
PubMed: 32547391
DOI: 10.3389/fphar.2020.00777