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Drug Development Research Jun 2021An artificial series of macrocycles based on 4,4'-sulfonyldiphenol intermediate was synthesized using a multistep procedure involving oxidation of bisphenol sulfide,...
An artificial series of macrocycles based on 4,4'-sulfonyldiphenol intermediate was synthesized using a multistep procedure involving oxidation of bisphenol sulfide, etherification of phenolic hydroxyl groups, and final ring closure with different diamines. Different chemical species having aromatic, heteroaromatic, and aliphatic characters were incorporated into macrocyclic frameworks in the final step of ring closure. This simple and easily executable synthetic strategy was applied to synthesize 15 macrocycles (5a-o) in excellent yields. Characterization of the synthesized products was achieved through well-known modern spectroscopic techniques such as IR, NMR, and Mass. Macrocycles 5m and 5n were found to show significant AChE inhibition with IC values of 76.9 ± 0.24 and 71.2 ± 0.77 μM, respectively. Macrocycle 5n was also found to be an active inhibitor of butyrylcholinesterase (BChE) with IC score of 55.3 ± 0.54 μM. Among others, macrocycle 5l cyclized with o-phenylenediamine demonstrated moderate inhibition with IC value of 81.1 ± 0.54 μM. Increasing interest in studying interactions of macrocycles with different enzymatic targets compelled us to design and synthesize sulfone-based macrocycles that might prove as highly potent class of biologically active compounds.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Macrocyclic Compounds; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship; Sulfones
PubMed: 33368483
DOI: 10.1002/ddr.21775 -
Bioorganic Chemistry Nov 2022As the vital component of innate immune system, the NLRP3 inflammasome is implicated in the onset and progression of a variety of inflammatory diseases and has emerged...
As the vital component of innate immune system, the NLRP3 inflammasome is implicated in the onset and progression of a variety of inflammatory diseases and has emerged as an attractive drug target. Herein a series of novel phenyl vinyl sulfone based NLRP3 inflammasome inhibitors were designed, synthesized and biologically characterized. The most potent two hits 7a and 5b showed inhibition on the NLRP3 inflammasome with the IC of 1.83 ± 0.28 µM and 0.91 ± 0.06 µM, respectively. Further characterization confirmed their inhibition of NLRP3-mediated IL-1β release in vivo. Collectively, our findings encourage further research of more potent inhibitors based on this chemical scaffold.
Topics: Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Sulfones
PubMed: 35914391
DOI: 10.1016/j.bioorg.2022.106010 -
Ecotoxicology and Environmental Safety Dec 2022Per- and polyfluoroalkyl substances (PFASs) are common environmental contaminants and are widely detected in humans. Previous studies have linked PFASs exposure to...
BACKGROUND
Per- and polyfluoroalkyl substances (PFASs) are common environmental contaminants and are widely detected in humans. Previous studies have linked PFASs exposure to adverse birth outcomes. However, the association between maternal exposure to PFASs and hemoglobin (Hb) and hematocrit (HCT) remains unclear.
OBJECTIVES
We aimed to explore the relationship between PFASs exposure with Hb and HCT during pregnancy.
METHODS
The present birth cohort study included 1044 pregnant women from Wuhan, China. Maternal HCT and Hb were measured in the first, second and third trimesters, and 13 PFASs were detected in the cord sera. Mixed linear models and general linear regression were applied to analyze the association between each single PFASs and Hb and HCT. Weighted quantile sum (WQS) regressions were used to investigate the association between PFASs mixture and Hb and HCT during pregnancy.
RESULTS
In single-PFAS models, 10 PFASs were positively associated with HCT and Hb across pregnancy (a 10-fold increase in PFASs was associated with 1.47-3.54 % change in HCT and 1.46-3.20 % change in Hb (All P-FDR < 0.05). In addition, Hb and HCT were more positively related to PFASs in the second and third trimesters rather than the first trimester. The association between PFASs exposure and maternal HCT and Hb was not significant in the iron supplementation group, whereas significant in the non-iron supplementation group. A significant interaction between iron supplementation and non-iron supplementation was also detected. WQS regressions showed that perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS) contributed most to the association between PFASs and HCT and Hb in the second and third trimesters, respectively.
CONCLUSION
Maternal PFASs exposure was positive with serum Hb and HCT. Moreover, maternal iron supplementation may play a modifying effect in influencing the relationship between PFASs and HCT and Hb.
Topics: Pregnancy; Female; Humans; Hematocrit; Fluorocarbons; Cohort Studies; Hemoglobins; Alkanesulfonates
PubMed: 36423372
DOI: 10.1016/j.ecoenv.2022.114319 -
Chemical Communications (Cambridge,... Jun 2023A photocatalyzed heteroarene-migratory dithiosulfonylation of alkene-tethered sulfone using dithiosulfonate (ArSO-SSR) has been reported, featuring mild conditions, and...
A photocatalyzed heteroarene-migratory dithiosulfonylation of alkene-tethered sulfone using dithiosulfonate (ArSO-SSR) has been reported, featuring mild conditions, and high atom economy. The resulting products can be converted into dihydrothiophenes and homoallyl disulfides, making the method highly valuable.
Topics: Disulfides; Alkenes; Light; Sulfones
PubMed: 37222470
DOI: 10.1039/d3cc01994b -
Molecular and Biochemical Parasitology Dec 2023Acanthamoeba are known to cause a vision threatening eye infection typically due to contact lens wear, and an infection of the central nervous system. The ability of...
Acanthamoeba are known to cause a vision threatening eye infection typically due to contact lens wear, and an infection of the central nervous system. The ability of these amoebae to switch phenotypes, from an active trophozoite to a resistant cyst form is not well understood; the cyst stage is often resistant to chemotherapy, which is of concern given the rise of contact lens use and the ineffective disinfectants available, versus the cyst stage. Herein, for the first time, a range of raloxifene sulfonate/sulfamate derivatives which target nucleotide pyrophosphatase/phosphodiesterase enzymes, were assessed using amoebicidal and excystation tests versus the trophozoite and cyst stage of Acanthamoeba. Moreover, the potential for cytopathogenicity inhibition in amoebae was assessed. Each of the derivatives showed considerable anti-amoebic activity as well as the ability to suppress phenotypic switching (except for compound 1a). Selected raloxifene derivatives reduced Acanthamoeba-mediated host cell damage using lactate dehydrogenase assay. These findings suggest that pyrophosphatase/phosphodiesterase enzymes may be valuable targets against Acanthamoeba infections.
Topics: Animals; Acanthamoeba castellanii; Raloxifene Hydrochloride; Sulfonic Acids; Trophozoites; Alkanesulfonates; Phosphoric Diester Hydrolases
PubMed: 37562558
DOI: 10.1016/j.molbiopara.2023.111582 -
Journal of the American Chemical Society Mar 2020Photoactivation of bioactive molecules allows manipulation of cellular processes with high spatiotemporal precision. The recent emergence of visible-light excitable...
Photoactivation of bioactive molecules allows manipulation of cellular processes with high spatiotemporal precision. The recent emergence of visible-light excitable photoprotecting groups has the potential to further expand the established utility of the photoactivation strategy in biological applications by offering higher tissue penetration, diminished phototoxicity, and compatibility with other light-dependent techniques. Nevertheless, a critical barrier to such applications remains the significant hydrophobicity of most visible-light excitable photocaging groups. Here, we find that applying the conventional 2,6-sulfonation to -methyl BODIPY photocages is incompatible with their photoreaction due to an increase in the excited state barrier for photorelease. We present a simple, remote sulfonation solution to BODIPY photocages that imparts water solubility and provides control over cellular permeability while retaining their favorable spectroscopic and photoreaction properties. Peripherally disulfonated BODIPY photocages are cell impermeable, making them useful for modulation of cell-surface receptors, while monosulfonated BODIPY retains the ability to cross the cellular membrane and can modulate intracellular targets. This new approach is generalizable for controlling BODIPY localization and was validated by sensitization of mammalian cells and neurons by visible-light photoactivation of signaling molecules.
Topics: Alkanesulfonates; Animals; Boron Compounds; Cell Membrane; Dopamine; Drug Carriers; Fluorescent Dyes; HEK293 Cells; Hippocampus; Histamine; Humans; Light; Microscopy, Confocal; Microscopy, Fluorescence; Molecular Structure; Neurons; Rats; Solubility
PubMed: 32115942
DOI: 10.1021/jacs.9b13219 -
The Science of the Total Environment Mar 2023The extensive use of per- and polyfluorinated alkyl substances (PFASs) and their substitutes has resulted in their frequent detections in environmental matrices....
The extensive use of per- and polyfluorinated alkyl substances (PFASs) and their substitutes has resulted in their frequent detections in environmental matrices. However, limited information is known about their uptake into vegetables and health risk through diet, particularly for those emerging alternatives. In this study, a total of 17 PFASs (namely 12 legacy PFASs and 5 of their alternatives) were compared for their accumulation into four staple vegetables (lettuce, Chinese cabbage, chrysanthemum coronarium, and cucumber) in hydroponic system with single PFAS concentration being 10 μg/L, except for 8:2 chlorinated polyfluoroalkyl ether sulfonate (Cl-PFESA) as 0.5 μg/L. The sum concentrations of 17 PFASs in edible parts were in the order of Chinese cabbage leaf (13,456 ng/g) > lettuce leaf (5996 ng/g) > cucumber fruit (4115 ng/g) >chrysanthemum coronarium stem (3999 ng/g). For perfluorooctanoate acid (PFOA) and its alternatives, hexafluoropropylene oxide trimer acid (HFPO-TA) preferentially accumulated in roots than PFOA with root concentration factors being 35.7-99.9. Translocation to edible parts was more remarkable for hexafluoropropylene oxide dimer acid (HFPO-DA) compared with PFOA in lettuce and cucumber. For perfluorooctanesulfonate acid (PFOS) and its alternatives, roots of all the four vegetables were found to more readily accumulate 8:2 Cl-PFESA than PFOS, but 8:2 Cl-PFESA was hardly translocated to the aerial parts. Significantly (p < 0.05) higher edible concentrations of 8:2 and 6:2 fluorotelomer sulfonic acids (FTSA) than that of PFOS were observed for cucumber.
Topics: Vegetables; Hydroponics; Fluorocarbons; Alkanesulfonic Acids; Alkanesulfonates; Ethers; Ether; Brassica; China
PubMed: 36481150
DOI: 10.1016/j.scitotenv.2022.160684 -
Angewandte Chemie (International Ed. in... Oct 2022Nanoelectrochemistry allows for the investigation of the interaction of per- and polyfluoroalkyl substances (PFASs) with silver nanoparticles (AgNPs) and the elucidation...
Nanoelectrochemistry allows for the investigation of the interaction of per- and polyfluoroalkyl substances (PFASs) with silver nanoparticles (AgNPs) and the elucidation of the binding behaviour of PFASs to nanoscale surfaces with high sensitivity. Mechanistic studies supported by single particle collision electrochemistry (SPCE), spectroscopic and density functional theory (DFT) calculations indicate the capability of polyfluorooctane sulfonic acid (PFOS), a representative PFAS, to selectively bind and induce aggregation of AgNPs. Single-particle measurements provide identification of the "discrete" AgNPs agglomeration (e.g. 2-3 NPs) formed through the inter-particles F-F interactions and the selective replacement of the citrate stabilizer by the sulfonate of the PFOS. Such interactions are characteristic only for long chain PFAS (-SO ) providing a means to selectively identify these substances down to ppt levels. Measuring and understanding the interactions of PFAS at nanoscale surfaces are crucial for designing ultrasensitive methods for detection and for modelling and predicting their interaction in the environment.
Topics: Alkanesulfonates; Citrates; Fluorocarbons; Metal Nanoparticles; Silver; Water Pollutants, Chemical
PubMed: 35838332
DOI: 10.1002/anie.202209164 -
Environmental Science and Pollution... Oct 2023Per- and polyfluoroalkyl substances (PFASs) are a group of concerned persistent toxic substances, especially for their application or unintentional formation in food... (Review)
Review
Per- and polyfluoroalkyl substances (PFASs) are a group of concerned persistent toxic substances, especially for their application or unintentional formation in food contact materials (FCMs). However, information about the occurrence, sources, and fate of these pollutants in food packaging materials from Vietnam as well as Southeast Asian countries is probably still obscured. In this study, levels of 13 perfluoroalkyl carboxylic acids (PFCAs) and 4 sulfonates (PFSs) were determined in various types of food packaging samples collected from Vietnamese markets. Generally low concentrations of total 17 PFASs (median 0.341; max 624 ng/g) suggested that these compounds were mainly inadvertently produced rather than intentionally added to the packaging materials. A few mochi paper tray samples had relatively high PFAS levels (372-624 ng/g), which were dominated by long-chain (C-C) PFCAs. A comprehensive and updated overview of PFASs in FCMs from different countries in the world was also provided. Current database could not provide conclusive trends of PFAS concentrations and profiles in FCMs between continents and countries. The highest levels up to ppm were reported for PFCAs (e.g., PFBA, PFHxA, PFOA, and PFDA) and several fluorotelomer alcohols and carboxylic acids, while PFSs were almost absent in FCMs. FPASs can emit from FCMs, migrate to food, and then contribute to dietary exposure in humans and animals. Additional investigations on the occurrence, sources, behavior and fate, and impacts of PFASs in FCMs are critically needed, especially in emerging and developing countries.
Topics: Humans; Animals; Vietnam; Fluorocarbons; Water Pollutants, Chemical; Alkanesulfonates; Carboxylic Acids; Environmental Monitoring; Alkanesulfonic Acids
PubMed: 37698798
DOI: 10.1007/s11356-023-29746-5 -
Environmental Science & Technology Apr 2024Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is inevitable among pregnant women. Nevertheless, there is a scarcity of research...
Impact of Gestational Exposure to Individual and Combined Per- and Polyfluoroalkyl Substances on a Placental Structure and Efficiency: Findings from the Ma'anshan Birth Cohort.
Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is inevitable among pregnant women. Nevertheless, there is a scarcity of research investigating the connections between prenatal PFAS exposure and the placental structure and efficiency. Based on 712 maternal-fetal dyads in the Ma'anshan Birth Cohort, we analyzed associations between individual and mixed PFAS exposure and placental measures. We repeatedly measured 12 PFAS in the maternal serum during pregnancy. Placental weight, scaling exponent, chorionic disc area, and disc eccentricity were used as the outcome variables. Upon adjusting for confounders and implementing corrections for multiple comparisons, we identified positive associations between branched perfluorohexane sulfonate (br-PFHxS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) with placental weight. Additionally, a positive association was observed between br-PFHxS and the scaling exponent, where a higher scaling exponent signified reduced placental efficiency. Based on neonatal sex stratification, female infants were found to be more susceptible to the adverse effects of PFAS exposure. Mixed exposure modeling revealed that mixed PFAS exposure was positively associated with placental weight and scaling exponent, particularly during the second and third trimesters. Furthermore, br-PFHxS and 6:2 Cl-PFESA played major roles in the placental measures. This study provides the first epidemiological evidence of the relationship between prenatal PFAS exposure and placental measures.
Topics: Infant, Newborn; Infant; Humans; Female; Pregnancy; Placenta; Birth Cohort; Alkanesulfonates; Fluorocarbons; Alkanesulfonic Acids; Environmental Pollutants
PubMed: 38525964
DOI: 10.1021/acs.est.3c09611