Search

Secondary aluminum dross (SAD) is a solid waste of aluminum dross after it is extracted aluminum. Soda-lime-aluminosilicate (SLAS) glass-ceramics with high alumina contents (over 30 wt%) were successfully manufactured from SAD using pyrometallurgy without additional nucleation agents. The nucleation process of SLAS glass was studied, and 670 °C was selected as the nucleation temperature according to differential scanning calorimetry and X-ray diffraction results. Field-emission transmission electron microscopy was applied to study the microstructure of the specimens thermally treated at 670 °C for 3 and 12 h. Nucleation consisted of two parts: iron oxide nucleation and jadeite nucleation. During iron oxide nucleation, when the thermal treatment time increased from 3 to 12 h, the iron oxides first congregated in an amorphous phase and a small amount of metastable crystal; then, the congregated iron oxides crystallized into hematite and magnetite, which acted as crystal nuclei. During jadeite nucleation, the jadeite spontaneously crystallized from the glass matrix after thermal treatment at 670 °C. When the thermal treatment time increased from 3 to 12 h, the size of the jadeite crystals increased from approximately 6 to 12 nm. Jadeite crystals with a diameter of 12 nm acted as crystal nuclei. For glass-ceramics with a high content of aluminum and sodium, jadeite crystals can act as crystal nuclei without additional nucleation agents. [Display omitted] [ABSTRACT FROM AUTHOR]

• Room-temperature and robust C-N coupling methodology. • Discovered the promoting effect of alkane solvents. • Synthesis of morpholine and pirazine heterocycle derivatives. • Prepared amines showing in vitro antiproliferative activities. Polar solvents are often chosen for transition metal catalyzed C-N coupling reactions. In this work, it was found that the use of alkane solvents (e.g. cyclohexane, heptane) allows for highly efficient Ni-catalyzed C-N coupling of aryl pseudohalides with different types of amines in the presence of NHC ligands. Excellent functional group tolerance was achieved. Stronger hydrogen bonding effect between amine NH moiety and polar OTs/OTf in alkane solvents might be responsible for the high activity. Meanwhile, some of the obtained products showed in vitro antiproliferative activities. In this work, it was found that the use of alkane solvents allows for highly efficient Ni-catalyzed C-N coupling of aryl pseudohalides with different types of amines in the presence of NHC ligands. [Display omitted] [ABSTRACT FROM AUTHOR]

Surface modification of carbon nanotubes (CNTs) were performed by grafting of hydroxyl-terminated polydimethylsiloxane (HPDMS) covalently. The results of dissolution experiments revealed that long-time stable dispersions of HPDMS-functionalized CNTs (CNTs-HPDMS) were achieved in a range of solvents including ethanol, ethyl acetate, dimethylbenzene and cyclohexane, even after being placed for 3 months. Subsequently, CNTs-HPDMS were incorporated into poly(methylphenylsiloxane) (PMPS) matrix to prepare composites. Scanning electron microscopy analysis showed that CNTs-HPDMS had homogeneous dispersion and strong interfacial adhesion in PMPS, which led to much better mechanical properties of composites compared to those filled with untreated CNTs. Furthermore, the incorporation of CNTs-HPDMS significantly enhanced the thermal stability of PMPS composites both under nitrogen and air. The improved barrier effect of CNTs-HPDMS resulted from the better filler dispersion was considered to play a crucial role, which on the one hand suppressed the depolymerization of PMPS under nitrogen and on the other hand inhibited the oxygen diffusion in matrix under air. Besides, the hydroxyl groups of HPDMS could react with PMPS to form additional crosslinking during heating, and thus delayed the degradation of PMPS to some extent. [ABSTRACT FROM AUTHOR]

A wide range of studies have characterized different types of biosorbent, with regard to their interactions with chemicals. This has resulted in the development of poly-parameter linear free energy relationships (pp-LFERs) for the estimation of partitioning of neutral organic compounds to biological phases (e.g., storage lipids, phospholipids and serum albumins). The aims of this study were to explore and evaluate the influence of implementing pp-LFERs both into a one-compartment fish model and a multi-compartment physiologically based toxicokinetic (PBTK) fish model and the associated implications for chemical risk assessment. For this purpose, fish was used as reference biota, due to their important role in aquatic food chains and dietary exposure to humans. The bioconcentration factor (BCF) was utilized as the evaluation metric. Overall, our results indicated that models incorporating pp-LFERs (R 2 = 0.75) slightly outperformed the single parameter (sp) LFERs approach in the one-compartmental fish model (R 2 = 0.72). A pronounced enhancement was achieved for compounds with log K OW between 4 and 5 with increased R 2 from 0.52 to 0.71. The minimal improvement was caused by the overestimation of lipid contribution and underestimation of protein contribution by the sp-approach, which cancelled each other out. Meanwhile, a greater improvement was observed for multi-compartmental PBTK models with consideration of metabolism, making all predictions fall within a factor of 10 compared with measured data. For screening purposes, the K OW -based (sp-LFERs) approach should be sufficient to quantify the main partitioning characteristics. Further developments are required for the consideration of ionization and more accurate quantification of biotransformation in biota. [ABSTRACT FROM AUTHOR]

Bangladesh is one of the most populated countries in the world. Rapid industrialization and urbanization in the last decades have caused emission of pollutants in the environment. The aim of the study was to assess atmospheric 16 polycyclic aromatic hydrocarbons (Σ 16 PAH) in Bangladesh using PUF-PASs deployed in 5 metropolitan cities and one large non-metropolitan city from December 2017 to September 2018. Spatial distribution of Σ 16 PAH ranged from 3.6 ± 1.1 to 22.4 ± 6.9 ng/m3. The maximum concentration of 22.4 ± 6.69 ng/m3 was found on the site-23 (urban), a newly established metropolitan city. Reasonably, the lowest concentration (3.6 ± 1.1 ng/m3) was recorded at the rural site (site-7). Seasonal variation of ∑ 16 PAH was found to be 4.8–28.4, 2.2–12.0 and 2.7–30.5 ng/m3 in the winter, pre-monsoon and monsoon, respectively. Among the PAH isomers, phenanthrene, fluoranthene and pyrene significantly contributed to the total concentrations of PAHs with 30.4, 27.8 and 20.1% in the winter, 18.9, 29.4 and 21.9% in pre-monsoon and 14.2, 29.9 and 21.9% in monsoon, respectively. Seasonal variation of PAHs followed the decreasing order: winter > monsoon > pre-monsoon. Molecular weight-based results revealed that 4- and 3-rings PAHs (4-rings: 53–60%; 3-rings: 23–37%) mostly contributed to the total concentration of PAHs. Diagnostic ratios, PMF model and PCA results suggested that combustion of coal, petroleum, and incineration of biomass/plastics and municipal solid waste are the primary sources of PAHs in Bangladesh. Calculated BaP TEQ and BaP MEQ and ICR values were higher for the children than that of the adults. The higher values of the BaP TEQ and BaP MEQ and ICR compared to those suggested by the WHO and USEPA, imply that population of Bangladesh, particularly children, may be at high risk for health problems from PAHs. [Display omitted] • Monitoring of atmospheric PAHs using PUF-PASs in 6 metropolitan cities in Bangladesh. • High-way, urban, biomass-based combustion, dumping sites were highly contaminated. • Seasonal variation of PAHs follows decreasing order: winter > monsoon > pre-monsoon. • Combustion of coal, petroleum, biomass and municipal waste possible sources of PAHs. • Risk assessment shows high potential health risk caused by PAHs. [ABSTRACT FROM AUTHOR]

Black carbon (BC) is ubiquitous in the environment and is a significant component of the refractory carbon pool. However, its sources, biogeochemical processes, and environmental residence times are poorly understood. One important reason is that the technical protocols for isolating/analyzing BC vary across different matrices, thereby bringing inconsistency among studies on BC in different environment media. Benzene polycarboxylic acids (BPCA), produced by nitric acid oxidation of the condensed aromatic structure that is common in BC and BC-like substances, has been proven to be a useful molecular proxy for tracking BC in the Earth's surface. Here, we introduce a new technical approach for the compound-specific dual-carbon isotope (δ13C and Δ14C) analysis of BPCA. The BPCA compounds are isolated using preparative liquid chromatography, in which trifluoroacetic acid is used in the mobile phase instead of phosphoric acid. This allows complete removal of solvent from the isolated BPCA fraction, so that conversion of BPCA isolates into CO 2 can be done by conventional oxidation methods for off-line Δ14C analysis with accelerator mass spectrometry. Liquid chromatography (void column)-stable carbon isotope ratio mass spectrometry is employed to measure δ13C of the isolated BPCA, leaving as much BPCA carbon amount as possible for 14C analysis. Blockage of oxidation chamber due to incomplete oxidation of other organic acids in the samples is avoided thanks to preliminary isolation of BPCA. We tested the approach by applying it to solid and dissolved BC species in a suite of environmental reference materials, including maize char, coal, riverine natural organic matter (NOM 2R101N), marine sediment (SRM 1941b), urban dust (SRM 1649b), and coke-polluted soils. We assessed the offsets of BPCA-δ13C and BPCA-Δ14C values caused by procedural carbon contaminations to correct measured carbon isotopic values. Paired δ13C-Δ14C data of individual BPCA were plotted to validate and demonstrate the ability of this dual carbon isotope technique in tracking BC across different environmental matrices. We observed slightly different δ13C-Δ14C signatures among individual BPCA, indicating that the less condensed BC may have younger apparent radiocarbon ages. [Display omitted] • We outline a new approach for compound-specific δ13C-Δ14C analysis of BPCA. • Mobile phases of BPCA fractions isolated with HPLC are totally removed. • Validation using BC reference materials of various environmental media. [ABSTRACT FROM AUTHOR]

Total suspended particles (TSP) and gaseous samples were collected by using a high-volume sampler from March 2012 to March 2013 and January 2018 to January 2019 at a background site (Jinsha, JSH) in central China to study the chemical characteristics, seasonal variations, and potential sources of polycyclic aromatic hydrocarbons (PAHs). The average concentrations of ∑ 15 PAHs were 24.55 ± 9.19 ng m−3 in 2012/2013 and 20.98 ± 9.77 ng m−3 in 2018/2019. Low-ring PAHs were more concentrated in gas phase while high-ring PAHs were prone into particle phase. The concentrations of PAHs in the two sampling years were high in winter but low in summer and autumn. The relationships between the gas concentrations of PAHs and temperature indicated that most PAHs were influenced by long-range atmospheric transport (LRAT) in 2012/2013 and in 2018/2019, excluding anthracene (Ant) and pyrene (Pyr) were partially affected by air-surface re-volatilization in 2012/2013. The source of atmospheric PAHs at JSH was similar in 2012/2013 and 2018/2019,which was mainly due to the LRAT of PAHs emitted from biomass/fossil fuel combustion in the northern area of JSH. From 2012/2013 to 2018/2019, there was no significant difference between the concentrations of PAHs in spring and winter, whereas the concentrations of PAHs decreased from 2012/2013 to 2018/2019 in summer. In all, the control of PAHs at the source region was partially effective from 2012/2013 to 2018/2019. [Display omitted] • Atmospheric concentrations of PAHs at JSH in the two sampling years were both high in winter. • Mixture sources mainly contributed in 2012/2013, while combustion sources were dominant in 2018/2019. • Atmospheric PAHs at JSH were largely influenced by LRAT from the northern area of JSH in both 2012/2013 and 2018/2019. • The control of PAHs at source region was partly effective from 2012/2013 to 2018/2019. [ABSTRACT FROM AUTHOR]

• Glass ceramic foams with high strength is developed by multiple solid wastes. • Secondary aluminum ash as self-foaming material is proposed to prepare glass ceramic foams. • The self-foaming mechanism relies on the oxidation reaction of AlN. • The degree of polymerization in glass with different alkalinity is analyzed. Glass ceramic foam with high strength was developed using municipal waste incineration bottom ash, fly ash, pickling sludge and secondary aluminum ash as raw materials without foaming agent. The effect of the secondary aluminum ash content and alkalinity on the pore morphology, porosity, water absorption, compression strength and bulk density of glass ceramic foams has been evaluated. The results showed that the increase of secondary aluminum ash content is beneficial to gas generation, but it will reduce the formation of liquid phase, resulting in the variation of pore morphology. In the process of alkalinity adjustment, the degree of polymerization of glass decreased first and then increased, which is similar to the change of max pore size, providing guidance for quantitative analysis of pore formation. The optimized sample reached porosities up to 63.02%, bulk density of ~1.42 g/cm3, and excellent compressive strength ~41.93 MPa. The analysis of self-foaming mechanism proved that secondary aluminum ash can be used as a self-foaming waste results from the oxidation reaction of AlN. In this work, a clean and sustainable utilization method has been proposed for recycling multiple solid wastes by preparing glass ceramic foams with a potential application for construction insulation materials with load-bearing. Moreover, an innovative exploration of secondary aluminum ash as the self-foaming waste in high temperature environmental was proposed. [ABSTRACT FROM AUTHOR]

To discover broad spectrum antifungal agents, two strategies were applied, and a novel class of l -amino alcohol derivatives were designed and synthesized. 3-F substituted compounds 14i , 14n , 14s and 14v exhibited excellent antifungal activities with broad antifungal spectra against C. albicans and C. tropicalis , with MIC values in the range of 0.03–0.06 μg/mL, and against A. fumigatus and C. neoformans , with MIC values in the range of 1–2 μg/mL. Notably, Compounds 14i , 14n, 14s and 14v also displayed moderate activities against fluconazole-resistance strains 17# and CaR that were isolated from AIDS patients. Moreover, only compounds in the S -configuration showed antifungal activity. Preliminary mechanistic studies showed that the potent antifungal activity of compound 14v stemmed from inhibition of C. albicans CYP51. Compounds 14n and 14v were almost nontoxic to mammalian A549 cells, and their stability in human plasma was excellent. Image 1 • Compounds 14i , 14n, 14s and 14v exhibited excellent antifungal activities with broad antifungal spectra. • Compounds 14i , 14n, 14s and 14v showed moderate antifungal activities against fluconazole-resisitent Candida albicans. • l Compound 14v reduced the content of ergosterol in a dose-dependent manner. • l Compounds 14n and 14v were almost nontoxic to mammalian A549 cells. • Compound 14v showed excellent stability in human plasma. [ABSTRACT FROM AUTHOR]

Cytochromes P450 (CYPs) play an important role in the metabolism of endogenic and xenobiotic substances, especially drugs. In addition, many CYPs may serve as targets for disease treatment. However, due to the presence of a common heme, the hydrophobicity of the CYP binding cavity, and the high homology within the binding pocket, most CYP inhibitors lack selectivity, which often leads to drug-drug interactions. Therefore, it is meaningful to develop highly selective CYP inhibitors. In this review, we summarize some of the strategies that have been used to develop highly selective CYP inhibitors, such as the weakening of the heme-binding group interaction, reduction of molecular lipophilicity and introduction of small structural changes within compounds. [ABSTRACT FROM AUTHOR]

Polyaromatic organic matter (POM) is an important group of pollutants and light absorbers in ambient aerosols, which consists of a wide range of chemicals with fused benzene rings. POM in ambient aerosols is mainly derived from the incomplete combustion of fossil fuel and biomass. Source apportionment of POM is crucial for advising efficient mitigation of anthropogenic emissions, but that is a challenge due to the complicated composition of POM and ambient aerosols. Benzene polycarboxylic acids (BPCAs) have recently been introduced as molecular markers of atmospheric POM. Compound-specific radiocarbon analysis of BPCAs is expected to be a powerful tool for apportioning fossil sources and contemporary (i.e., biomass burning) sources of POM in ambient aerosols, yet this application is still lacking. We developed a method for radiocarbon analysis of BPCAs substituted with 3–6 carboxylic groups (B6CA, B5CA, B4CAs and B3CAs). BPCAs were isolated with preparative liquid chromatography with high recoveries (≥85%). The method is validated with reference materials with fossil and contemporary radiocarbon signatures. Successful radiocarbon analysis of BPCAs was achieved for these reference materials after correcting for the presence of average blanks (B6CA: 1.2 ± 0.2 μg, B5CA: 2.3 ± 0.6 μg, individual B4CAs: 2.7 ± 0.2 μg and individual B3CAs: 6.9 ± 0.7 μg). Source apportionment of POM based on radiocarbon analysis of BPCAs was performed for an urban dust reference material, as well as bulk aerosols and water-soluble, methanol-soluble fractions of ambient aerosols from a megacity of southern China. The results show varied contributions of fossil and contemporary sources among different POM fractions. [Display omitted] • Benzene polycarboxylic acids (BPCAs) are used to track polyaromatic organic matter (POM). • A method of compound-specific radiocarbon analysis (CSRA) of BPCAs is developed. • Successful CSRA of BPCAs is achieved for reference and ambient materials. • Sources of POM in ambient aerosols are apportioned by CSRA of BPCAs. • Fossil-contemporary source patterns vary between different POM fractions. [ABSTRACT FROM AUTHOR]

In this paper, novel three-dimensional (3D) CuO precursor was synthesized under the ice water bath. The flower-like micellar polyp-phenylenediamine (PpPD) was synthesized when the p-phenylenediamine-salicylic acid ([SA]/PPD) ratio was 1:1. The two amino groups of PpPD interacted with Cu by the coordination interactions. After calcination in the air, dandelion-like CuO nanoflowers were successfully prepared. The physicochemical properties of the as-prepared CuO were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), infrared spectrometer (FT-IR), UV-vis absorption spectra (UV-vis), and energy-dispersive spectrometer (EDS). In the participation of HO, the as-obtained CuO nanoflowers exhibited high efficiency on the decolorization of rhodamine B (RhB) by the synergy of ·OH and ·O . The novel dandelion-like CuO also provided more active sites to improve the photocatalytic effect. It can be applied to the degradation of dyes, such as RhB, and plays a role in environmental pollution control. [ABSTRACT FROM AUTHOR]

Black carbon (BC) is an important component of the brown clouds, contributing to climate and health effects of air pollution. In this work, we developed a new method for measuring BC concentrations and its radiocarbon isotope (14C) using quartz wool disk passive air samplers (Pas-QW). A field calibration study was conducted at two sampling sites (Guangzhou and Yantai), using an improved thermal/optical method to measure BC. Uptake profiles of Pas-QW were linear over the 77 days that the samplers were deployed, and the average sampling rate of BC measured was 1.1 ± 0.2 m3/day. The method was found to be reproducible with coefficients of variation as low as 17% for BC measured in ambient passive samples. Furthermore, passive sampling was carried out at six sites in the Indo-China Peninsula (ICP) from January to April and June to September of 2016. The high BC concentrations and the high fraction of modern carbon (f M) values emphasizes that ICP is still dominated by biomass burning emissions (residential cooking and agricultural burning), both in dry and wet seasons. This study provides a proof concept and methodology for the application of Pas-QW to cost-effectively expand measurements of BC at the global scale. [Display omitted] • A new method for measuring BC and its 14C using quartz wool disk passive samplers. • The method requires no sample processing and have good reproducibility for BC. • The relative contribution of biomass burning to BC can reach 67 ± 13% in ICP, with obvious spatiotemporal heterogeneity. [ABSTRACT FROM AUTHOR]

Cholesteryl ester transfer protein (CETP) is a potential target for cardiovascular disease therapy as inhibition of CETP leads to increased HDL-C in humans. Based on the structure of Merck's biphenyl CETP inhibitor, we designed novel N , N -substituted-cycloalkenyl-methylamine scaffold derivatives by utilizing core replacement and conformational restriction strategies. Consequently, twenty-eight compounds were synthesized and evaluated for their inhibitory activity against CETP. Their preliminary structure-activity relationships (SARs) studies indicate that polar substituents were tolerated in moiety A and hydrophobic alkyl groups at the 5-position of cyclohexene were critical for potency. Among them, compound 17a , bearing an N -(5-pyrazolyl-pyrimidin-2-yl)-cycloalkenyl- methylamine scaffold, exhibited excellent CETP inhibitory activity (IC 50 = 0.07 μM) in vitro . Furthermore, it showed an acceptable pharmacokinetic profile in S-D rats and efficient HDL-C increase in high-fat fed hamsters. [ABSTRACT FROM AUTHOR]

[Display omitted] Field-based sampling can provide more accurate evaluation than MODIS in regional biomass burning (BB) emissions given the limitations of MODIS on unresolved fires. Polyurethane foam-based passive air samplers (PUF-PASs) are a promising tool for collecting atmospheric monosaccharides. Here, we deployed PUF-PASs to monitor monosaccharides and other BB-related biomarkers and presented a dataset of 31 atmospheric BB-related biomarkers in the Indo-China Peninsula (ICP) and Southwest China. The peak concentrations of monosaccharides in the ICP occurred before monsoon season. The highest concentrations were in the eastern Mekong plain, while the lowest were along the eastern coast. BB-related biomarkers displayed elevated concentrations after April, particularly in the monsoon season; however, fewer active fires were recorded by MODIS. This revealed the importance of MODIS unresolved fires (e.g., indoor biofuel combustion, small-scale BB incidents, and charcoal fires) to the regional atmosphere. The PAS derived levoglucosan concentrations indicated that, with the inclusion of MODIS unresolved fires, the estimated top-down emissions of PM (4194–4974 Gg/yr), OC (1234–1719 Gg/yr) and EC (52–384 Gg/yr) would be higher than previous bottom-up estimations in the ICP. Future studies on these MODIS unresolved fires and regional monitoring data of BB are vital for improving the modeling of regional BB emissions. [ABSTRACT FROM AUTHOR]

A series of N , N -3-phenyl-3-benzylaminopropanamide derivatives were identified as novel CETP (cholesteryl ester transfer protein) inhibitors. In our previous study, lead compound L10 was discovered by pharmacophore-based virtual screening (Dong-Mei Zhao et al., 2014). Based on L10 (IC 50 8.06 μM), compound HL6 (IC 50 10.7 μM) was discovered following systematic structure variation and biological tests. Further optimization of the structure–activity relationship (SAR) resulted in N , N -3-phenyl-3-benzylaminopro panamides derivatives as novel CETP inhibitors. They were synthesized and evaluated against CETP by BODIPY-CE fluorescence assay. Among them, HL16 (IC 50 0.69 μM) was a highly potent CETP inhibitor in vitro. In addition, HL16 exhibited favorable HDL-C enhancement and LDL-C reduction in vivo by hamster. The molecular docking of HL16 into the CETP was performed. The binding mode demonstrated that HL16 occupied the CETP binding site and formed interactions with the key amino acid residues. [ABSTRACT FROM AUTHOR]

In this paper, we demonstrated a fluorescent o-phenylenediamine–m-phenylenediamine copolymer sensing system, which was synthesized by a facile and one-step hydrothermal method. The copolymer was first used as fluorescent probe for the detection of Chromium(VI) ion (Cr 6+ ) and showed high selectivity and sensitivity. The detection limit was 1×10 −11 M. It showed excellent linear relationships in wide range of 7×10 −11 –6×10 −10 M. Moreover, the addition of ethylenediaminetetraacetate (EDTA) to the detection system could successfully combine with Cr 6+ to form metal chelates, making the fluorescence recovery of o-phenylenediamine–m-phenylenediamine copolymer. What is important, the prepared process had no addition of initiating agent. [ABSTRACT FROM AUTHOR]

To discover antifungal compounds with broad-spectrum and stable metabolism, a series of 2-(benzo[ b ]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives was designed and synthesized. Compounds A30-A34 exhibited excellent broad-spectrum antifungal activity against Candida albicans with MIC values in the range of 0.03–0.5 μ g/mL, and against Cryptococcus neoformans and Aspergillus fumigatus with MIC values in the range of 0.25–2 μ g/mL. In addition, compounds A31 and A33 showed high metabolic stability in human liver microsomes in vitro , with the half-life of 80.5 min and 69.4 min, respectively. Moreover, compounds A31 and A33 showed weak or almost no inhibitory effect on the CYP3A4 and CYP2D6. The pharmacokinetic evaluation in SD rats showed that compound A31 had suitable pharmacokinetic properties and was worthy of further study. [Display omitted] • A novel class of 2-(benzo[ b ]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives was designed and synthesized. • Compounds A30 - A34 exhibited excellent broad-spectrum antifungal activities. • Compounds A31 and A33 showed weak inhibitory effect on CYP3A4 and CYP2D6. • Compound A31 showed high metabolic stability in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Airborne particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) are significant contributors leading to many human health issues. Thus, this study was designed to perform chemical analysis and biological impact of airborne particulate matter 10 (PM 10) in the World heritage City of Kandy City in Sri Lanka. 12 priority PAHs and 34 metals, including 10 highly toxic HMs were quantified. The biological effects of organic extracts were assayed using an in vitro primary porcine airway epithelial cell culture model. Cytotoxicity, DNA damage, and gene expressions of selected inflammatory and cancer-related genes were also assessed. Results showed that the total PAHs ranged from 3.062 to 36.887 ng/m3. The metals were dominated by Na > Ca > Mg > Al > K > Fe > Ti, while a few toxic HMs were much higher in the air than the existing ambient air quality standards. In the bioassays, a significant cytotoxicity (p < 0.05) was observed at 300 μg/mL treatment, and significant (p < 0.05) DNA damages were noted in all treatment groups. All genes assessed were found to be significantly up-regulated (p < 0.05) after 24 h of exposure and after 48 h, only TGF-β1 and p53 did not significantly up-regulate (p < 0.05). These findings confirm that the Kandy city air contains potential carcinogenic and mutagenic compounds and thus, exposure to Kandy air may increase the health risks and respiratory tract-related anomalies. • First comprehensive analysis and exposure assessment supported by bioassays for airborne PAHs and heavy metals in Sri Lanka. • Few PAH and heavy metal levels in the Kandy city air are above maximum permissible levels. • The compounds in the Kandy city air have inflammatory, carcinogenic and mutagenic potentials. • Immediate attention is required to establish emission control and safeguard the quality of air in Kandy city, Sri Lanka. [ABSTRACT FROM AUTHOR]

l -amino alcohol derivatives exhibited high antifungal activity, but the metabolic stability of human liver microsomes in vitro was poor, and the half-life of optimal compound 5 was less than 5 min. To improve the metabolic properties of the compounds, the scaffold hopping strategy was adopted and a series of antifungal compounds with a dihydrooxazole scaffold was designed and synthesized. Compounds A33-A38 substituted with 4-phenyl group on dihydrooxazole ring exhibited excellent antifungal activities against C. albicans , C. tropicalis and C. krusei , with MIC values in the range of 0.03–0.25 μ g/mL. In addition, the metabolic stability of compounds A33 and A34 in human liver microsomes in vitro was improved significantly, with the half-life greater than 145 min and the half-life of 59.1 min, respectively. Moreover, pharmacokinetic studies in SD rats showed that A33 exhibited favourable pharmacokinetic properties, with a bioavailability of 77.69%, and half-life (intravenous administration) of 9.35 h, indicating that A33 is worthy of further study. [Display omitted] • A novel class of dihydrooxazole compounds was designed and synthesized. • Compounds A33 - A38 showed excellent antifungal activities. • The metabolic stability of compounds A33 and A34 was improved dramatically. • Compound A33 exhibited favourable pharmacokinetic properties in SD rats. [ABSTRACT FROM AUTHOR]

Secondary aluminum dross (SAD) from aluminum industry is classified as a hazardous solid waste due to containing aluminum nitride (AlN). In this work, AlN was first used to reduce heavy metals by pyrometallurgy. The reduction rates for iron, chromium and nickel were up to 90%, 80% and 100%, respectively. However, the reduction from AlN and oxygen oxidization of AlN occurred simultaneously. AlN which formed solid solution with alumina could reduce heavy metals, while the rest was oxidized by oxygen. In addition, the reduction rates for iron and chromium could be increased with increasing CaF 2 from 6.7 to 9.0 wt%. CaF 2 could decreased viscosity of molten slag, which favored the ion migration, and then increased the reduction rates. After the reduction, glass ceramics were manufactured from the molten slags. The bending strength, microhardness and alkali resistance of the glass ceramics were up to 77 MPa, 1011 HV and 98.7%, respectively. According to XRD and SEM results, glass ceramics with CaAl 2 SiO 6 crystal phase, crosslinked network structure grains and smaller pores exhibited better bending resistance. In addition, glass ceramics with CaAl 2 SiO 6 crystal phase possessed the highest microhardness and alkali resistance. After this process, hazardous pickling sludge and SAD were totally recycled. [Display omitted] • Hazardous pickling sludge and SAD were totally recycled by pyrometallurgy. • AlN in SAD was first used to reduce heavy metals. • Reduction rates for iron, chromium and nickel were 90%, 80% and 100%. • Bending strength and microhardness of the glass ceramics were 77 MPa and 1011 HV. [ABSTRACT FROM AUTHOR]

A series of β-azole-phenylacetone derivatives with novel structures were designed and synthesized to combat the increasing incidence of susceptible fungal infections and drug-resistant fungal infections. The antifungal activity of the synthesized compounds was assessed against five susceptible strains and five fluconazole-resistant strains. Antifungal activity tests showed that most of the compounds exhibited excellent antifungal activities against five pathogenic strains with MIC values in the range of 0.03–1 μ g/mL. Compounds with R1 = 3-F substituted and 15o and 15ae exhibited moderate antifungal activities against fluconazole-resistant strains 17# and CaR with MIC values in the range of 1–8 μ g/mL. Compounds with R1 = H or 2-F (such as 15a , 15o , 15p) displayed moderate to good antifungal activity against fluconazole-resistant strains 632 , 901 and 904 with MIC values in the range of 0.125–4 μ g/mL. Notably, 15o and 15ae exhibited antifungal activity against five susceptible strains and five fluconazole-resistant strains. Preliminary mechanistic studies showed that the potent antifungal activity of compound 15ae stemmed from inhibition of C. albicans CYP51. Compounds 15o , 15z and 15ae were nearly nontoxic to mammalian A549 cells. Image 1 • 32 new compounds of β-Azole-phenylacetone derivatives were designed and synthesized. • Compounds 15a , 15b and 15u - ae exhibited excellent antifungal activities against five susceptible pathogenic strains. • Compound 15o showed moderate antifungal activities against five fluconazole-resistant Candida albicans. • Compound 15ae can reduce the content of ergosterol. • Compounds 15o , 15z , and 15ae were nearly nontoxic to mammalian A549 cells. [ABSTRACT FROM AUTHOR]

Pesticides play a crucial role in securing global food production to meet increasing demands. However, because of their pervasive use, they are now ubiquitous environmental pollutants that have adverse effects on both ecosystems and human health. In this study, the environmental occurrence and fate of 16 current-use pesticides (CUPs) were investigated in 93 forest soil samples obtained from 11 distinct mountains in China. The concentrations of the target pesticides ranged from 0.36 to 55 ng/g dry weight. Cypermethrin, dicofol, chlorpyrifos, chlorothalonil, and trifluralin were the most frequently detected CUPs. The CUP concentrations were generally higher in the O-horizon than in the A-horizon. Chlorpyrifos, chlorothalonil, and dicofol were detected in most deep layers in soil profiles from three mountains selected to represent distinct climate zones. No clear altitudinal trend in organic carbon-normalized concentrations of CUPs was observed in the O- or A-horizons within individual mountains. A negative correlation was noted between the CUP concentrations and the altitudes across all sampling sites. This indicated that proximity to emission sources was a key factor affecting the spatial distribution of CUPs in mountain forest soil on a national scale. The ecological risk assessment showed that dicofol and cypermethrin pose potential risks to earthworms. This study emphasizes the importance of source control when setting management strategies for CUPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the material basis, targets and molecular mechanism of Scutellariae Radix against periodontitis to provide theoretical basis for clinical applications., Materials and Methods: The active compounds and targets of Scutellariae Radix were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, and the periodontitis-related targets were collected by integrating Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), Genecards and Gene Expression Omnibus (GEO) database together. The potential targets of Scutellariae Radix against periodontitis were obtained from the intersection of two target sets. Metascape database was used for Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Discovery Studio software was used for molecular docking between key targets and compounds to evaluate their binding affinity. Western blot was used to check the expression of PTGS2 and MMP9 to verify the regulatory effects of baicalein, the main active compound of Scutellariae Radix , on human periodontal ligament stem cells (hPDLSCs) cultured under inflammatory environment which induced by lipopolysaccharide (LPS)., Results: 15 active compounds of Scutellariae Radix and 53 common targets for periodontitis treatment were identified. Among these targets, the 10 core targets were AKT1, IL-6, TNF, VEGFA, TP53, PTGS2, CASP3, JUN, MMP9 and HIF1A. GO and KEGG analysis mainly focused on response to LPS and pathways in cancer. Molecular docking showed that the main active compounds had good binding affinity with key targets. Cell experiments confirmed that baicalein can interfere the expression of pro-inflammatory factors PTGS2 and MMP9 proteins and exert anti-inflammatory effects., Conclusion: Current study preliminarily analyzed the mechanism of Scutellariae Radix against periodontitis, which provide a new idea for the utilization of Scutellariae Radix and the development of novel medicine for the clinical treatment of periodontitis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

The production and use of intentionally-produced polychlorinated biphenyls (PCBs) in China have a short history compared with countries of North America and Europe, where technical PCB mixtures were manufactured in large amounts for decades before being banned. Unintentionally-produced PCB emissions increased dramatically in China, leading to unique profiles of PCB burdens. This study first time evaluated 208 individual PCB congeners at 94 sites from surface sediments of the East China Marginal Seas (ECMSs) and explored their sources. Non-technical PCBs transported from atmospheric transport and river discharge played a dominant role in most areas of the ECMSs, while historical residuals of technical PCBs occupied the fine-grained sediments in muddy areas of the central Yellow Sea (YS), regarding to the low sedimentation rate in the central YS. Furthermore, emissions from Taizhou located on the coast of the East China Sea (ECS), which is an important electronic waste dismantling site in East China, contributed additional technical PCBs to the inner shelf of the ECS. Our results indicate that non-technical PCBs have become the dominant PCB species in the ECMSs, and emphasize the synergistic effects of large riverine input, long-range atmospheric transport, and muddy shelf deposition on PCB source and sink of in marginal seas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Plant height is a key agronomic trait that affects yield and is controlled by both phytohormone gibberellin (GA) and ultraviolet-B (UV-B) irradiation. However, whether and how plant height is modulated by UV-B-mediated changes in GA metabolism are not well understood. It has not been reported that the E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) is involved in the regulation of plant growth in response to environmental factors. We perform a forward genetic screen in soybean and find that a mutation in Glycine max Increased Leaf Petiole Angle1 (GmILPA1), encoding a subunit of the APC/C, lead to dwarfism under UV-B irradiation. UV-B promotes the accumulation of GmILPA1, which ubiquitinate the GA catabolic enzyme GA2 OXIDASE-like (GmGA2ox-like), resulting in its degradation in a UV-B-dependent manner. Another E3 ligase, GmUBL1, also ubiquitinate GmGA2ox-like and enhance the GmILPA1-mediated degradation of GmGA2ox-like, which suggest that GmILPA1-GmGA2ox-like module counteract the UV-B-mediated reduction of bioactive GAs. We also determine that GmILPA1 is a target of selection during soybean domestication and breeding. The deletion (Indel-665) in the promoter might facilitate the adaptation of soybean to high UV-B irradiation. This study indicates that an evolutionary GmILPA1 variant has the capability to develop ideal plant architecture with soybean cultivars., (© 2023. Springer Nature Limited.)

Aerosol black carbon (BC) is a short-lived climate pollutant. The poorly constrained provenance of tropical marine aerosol BC hinders the mechanistic understanding of extreme climate events and oceanic carbon cycling. Here, we collected PM 2.5 samples during research cruise NORC2016-10 through South China Sea (SCS) and Northeast Indian Ocean (NEIO) and measured the dual-carbon isotope compositions (δ 13 C- Δ 14 C) of BC using hydrogen pyrolysis technique. Aerosol BC exhibits six different δ 13 C- Δ 14 C isotopic spaces (i.e., isotope provinces). Liquid fossil fuel combustion, from shipping emissions and adjacent land, is the predominant source of BC over isotope provinces "SCS close to Chinese Mainland" (53.5%), "Malacca Strait" (53.4%), and "Open NEIO" (40.7%). C 3 biomass burning is the major contributor to BC over isotope provinces "NEIO close to Southeast Asia" (55.8%), "Open NEIO" (41.3%), and "Open SCS" (40.0%). Coal combustion and C 4 biomass burning show higher contributions to BC over "Sunda Strait" and "Open SCS" than the others. Overall, NEIO near the Bay of Bengal, Malacca Strait, and north SCS are three hot spots of fossil fuel-derived BC; the first two areas are also hot spots of biomass-derived BC. The comparable δ 13 C- Δ 14 C between BC in aerosol and dissolved BC in surface seawater may suggest atmospheric BC deposition as a potential source of oceanic dissolved BC.

This study was designed to assess the distribution of organochlorines (OCs) in fish species, their spatio-temporal variations, bioaccumulation potential, and associated human health risks via dietary intake. The levels of twenty-three organochlorine pesticides (OCPs) and thirty-five polychlorinated biphenyls (PCBs) were analyzed in six fish species collected from the riverine ecosystem of Punjab Province, Pakistan. The results indicated that the mean levels of Σ 23 OCPs were 74.1 ng/g ww and 184 ng/g ww, and for Σ 35 PCBs the levels were 38.8 ng/g ww and 74.8 ng/g ww in herbivorous and carnivorous fish species, respectively. The most abundant contaminants in all fish species were DDTs (65%) and HCHs (14%) among OCPs and heavier PCB congeners (62%) among PCBs. As for dioxin-like PCBs, the WHO toxic equivalency values (ng TEQ/g ww) were in the range of 0.21 (Cyprinus Carpio) to 2.38 (Rita Rita), exceeding the maximum allowable limit of 0.004 ng TEQ/g, ww by the European Commission. Spatio-temporal analysis indicated relatively higher OC levels in winter season with elevated concentrations in fish samples from industrial zone. The bioconcentration factor (L/kg) values ranged from 723 to 2773 for PCBs and 315 to 923 for OCPs in all fish species, with higher levels were reported in carnivorous species. The human health risk assessment at both 50th and 95th percentiles revealed the absence of any significant non-carcinogenic risk as calculated HR was less than 1. However, the critical carcinogenic risk was found to be associated for most of the contaminants, signifying the dietary exposure to OCPs and PCBs might pose the public health concern., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of the present study was to determine the occurrence, spatio-temporal variations, source apportioning, and ecological risk assessment of selected PCBs and OCPs in surface water and sediments collected riverine environment of Punjab province, Pakistan. The concentration of ΣOCPs (water: 64-455 ng/L; sediments: 117-616 ng/g) and ΣPCBs (water: 2-132 ng/L; sediments: 3.27-200 ng/g) was found comparatively higher than the levels reported from other parts of the world. The higher concentrations of DDTs and HCHs were detected in both studied matrices, whereas among PCBs, CB-28, 49 and CB-37, 82 were dominant in water and sediments, respectively. The isomeric ratios including α-HCH/γ-HCH, (DDE + DDD) / DDTs, and α /β-endosulfan reflected the recent use of lindane, technical DDT, and endosulfan in the study area. The WHO-TEQ values of DL-PCBs ranged from 3.6 × 10 -6 to 0.115 ng/L and 8.7 × 10 -6 to 0.157 ng/g in surface water and sediments in both seasons, respectively. The spatial variation analysis revealed that the sites in the industrial and agricultural zones were highly contaminated. The OCPs and PCBs fluxes to downstream areas were estimated to be 12.4 tons/year and 1.9 tons/year, respectively. The significant ecological risks were estimated to be posed by OCPs and PCBs, as their levels in 67% and 62% of surface water and sediment samples were exceeding the threshold limits, highlighting effects to ecological integrities., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Biomass burning (BB) is an important source of atmospheric persistent organic pollutants (POPs) across the world. However, there are few field-based regional studies regarding the POPs released from BB. Due to the current limitations of emission factors and satellites, the contribution of BB to airborne POPs is still not well understood. In this study, with the simultaneous monitoring of BB biomarkers and POPs based on polyurethane foam-based passive air sampling technique, we mapped the contribution of BB to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in the Indo-China Peninsula. Spearman correlations between levoglucosan and 16 PCBs ( r s = 0.264-0.767, p < 0.05) and 2 OCPs ( r s = 0.250-0.328, p < 0.05) confirmed that BB may facilitate POP emissions. Source apportionment indicated that BB contributed 9.3% to the total PCB and OCP mass. The high contribution of positive matrix factorization-resolved BB to PCBs and OCPs was almost consistent with their concentration distributions in the open BB season but not completely consistent with those in the pre-monsoon and/or monsoon seasons. Their contribution distributions may reflect the use history and geographic distribution in secondary sources of POPs. The field-based contribution dataset of BB to POPs is significant in improving regional BB emission inventories and model prediction.

Wearing of vehicle parts could release many chemical additives into the environment, such as benzotriazoles (BTRs), benzothiazoles (BTHs), and p-phenylenediamines (PPDs), which are potentially toxic to wildlife and humans. This study investigated the occurrence, source, and risks of BTRs, BTHs, and PPDs in a source catchment providing water to Guangzhou, a megacity in South China, covering groundwater, surface water, and stormwater. The results showed that BTRs and BTHs were predominant in surface water and groundwater. Unexpectedly, the BTR and BTH concentrations were lower in surface water than groundwater in a third of the paired samples. For the first time, 6PPD-quinone, a toxic ozonation product of N-(1,3-dimethylbutyl)-N'-phenyl-1,4-phenylenediamine (6PPD), was extensively detected in source waters. Stormwater decreased the BTR concentrations but increased the 6PPD-quinone concentrations in surface water owing to their affiliation to suspended particles. From natural to urban segments of Liuxi river, a downstream increasing trend in BTR and BTH concentrations was observed, confirming that they are indicative of urban anthropogenic activities. Strong correlations between industrial activities and BTR or BTH concentrations in surface water indicated that industrial activities were their main sources. Six compounds were prioritized as potentially persistent, mobile, and toxic (PMT) chemicals, combing our monitoring results and REACH criterion. This study improves our understanding of the environmental fates and risks of water-soluble tire-wear chemicals, which provides important information for chemical management, and indicates attention should be paid to the risk posed by 6PPD-quinone in the source water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The global incidence rate of non-alcoholic fatty liver disease (NAFLD) is approximately 25%. With the global increase in obesity and its associated metabolic syndromes, NAFLD has become an important cause of chronic liver disease in many countries. Despite recent advances in pathogenesis, diagnosis, and therapeutics, there are still challenges in its treatment. In this review, we briefly describe diagnostic methods, therapeutic targets, and drugs related to NAFLD. In particular, we focus on evaluating carbohydrate and lipid metabolism, lipotoxicity, cell death, inflammation, and fibrosis as potential therapeutic targets for NAFLD. We also summarized the clinical research progress in terms of drug development and combination therapy, thereby providing references for NAFLD drug development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fu, Zhou, Shen, Li, Zhang, Cui, Zhang, Li, Chen, Zhao, Li and Ye.)

Incomplete understanding of the sources of secondary organic aerosol (SOA) leads to large uncertainty in both air quality management and in climate change assessment. Chemical reactions occurring in the atmospheric aqueous phase represent an important source of SOA mass, yet, the effects of anthropogenic emissions on the aqueous SOA (aqSOA) are not well constrained. Here we use compound-specific dual-carbon isotopic fingerprints (δ 13 C and Δ 14 C) of dominant aqSOA molecules, such as oxalic acid, to track the precursor sources and formation mechanisms of aqSOA. Substantial stable carbon isotope fractionation of aqSOA molecules provides robust evidence for extensive aqueous-phase processing. Contrary to the paradigm that these aqSOA compounds are largely biogenic, radiocarbon-based source apportionments show that fossil precursors produced over one-half of the aqSOA molecules. Large fractions of fossil-derived aqSOA contribute substantially to the total water-soluble organic aerosol load and hence impact projections of both air quality and anthropogenic radiative forcing. Our findings reveal the importance of fossil emissions for aqSOA with effects on climate and air quality., (© 2022. The Author(s).)

Cyano-containing compounds constitute important pharmaceuticals, agrochemicals and organic materials. Traditional cyanation methods often rely on the use of toxic metal cyanides which have serious disposal, storage and transportation issues. Therefore, there is an increasing need to develop general and efficient catalytic methods for cyanide-free production of nitriles. Here we report the reductive cyanation of organic chlorides using CO 2 /NH 3 as the electrophilic CN source. The use of tridentate phosphine ligand Triphos allows for the nickel-catalyzed cyanation of a broad array of aryl and aliphatic chlorides to produce the desired nitrile products in good yields, and with excellent functional group tolerance. Cheap and bench-stable urea was also shown as suitable CN source, suggesting promising application potential. Mechanistic studies imply that Triphos-Ni(I) species are responsible for the reductive C-C coupling approach involving isocyanate intermediates. This method expands the application potential of reductive cyanation in the synthesis of functionalized nitrile compounds under cyanide-free conditions, which is valuable for safe synthesis of (isotope-labeled) drugs.

To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compound 1, a series of benzoheterocycle analogues were designed, synthesized and evaluated for their in vitro antifungal activity. The most promising compounds 13s and 14a exhibited excellent antifungal activity against C. albicans, C. neoformans, A. fumigatus and fluconazole-resistant C. albicans strains, that was superior or comparable to those of the reference drugs fluconazole and voriconazole. GC-MS analyses suggested that the novel compound 13s might have a similar mechanism to fluconazole by inhibiting fungal lanosterol 14α-demethylase (CYP51). Furthermore, compounds 13s and 14a exhibited low inhibition profiles for various human cytochrome P450 isoforms as well as excellent blood plasma stability., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The mobility of arsenic (As) in soil depends on its sorption/desorption processes on soil particles. Plant uptake locally lowers As concentration in soil pore water, which would trigger resupplies of As from soil solid phase. To better understand the fate of As in soil system after its inputs into soil and its subsequent dynamic processes, diffusive gradients in thin films (DGT) technique along with DGT-induced fluxes in soils (DIFS) model were introduced to study the kinetic information of As in soils, including its response time (T C ) and resupply rate constant (k -1 ). To achieve a series of soils with gradient As level, two different types of soils with similar As level (total As in soil JL is 7.4 mg kg -1 , while in soil BJ is 6.5 mg kg -1 ) were collected and amended with exogenous As. Then, DGT deployments were carried out following a period of 90-day soil incubation. The simulated T C values in non-amended soil JL and soil BJ were 0.036 and 0.001 s -1 , respectively. The difference may due to the properties of these two soils, including pH values and contents of adsorption materials, such as Fe and Al compounds. After As inputs into soils, the intrinsic rate of As release from the solid phase to the solution phase in As-amended JL soil was much higher than that in non-amended soil. While for soil BJ, a decreasing trend was observed after As spiking. The redistribution of As may responsible for the different variation trends of As kinetics in these two soils after As spiking. The results indicated that the distribution coefficient of As (K d ) in soil was mainly affected by soil Olsen-P content due to an ubiquitous competition between P and As on soil particles.

To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (1), a series of aromatic heterocyclic derivatives were designed, synthesized and evaluated for in vitro antifungal activity. Many of the target compounds showed good inhibitory activity against Candida albicans and Cryptococcus neoformans. In particular, the isoxazole nuclei were more suited for improving the activity against Aspergillus spp. Among these compounds, 2-F substituted analogues 23g and 23h displayed the most remarkable in vitro activity against Candida spp., C. neoformans, A. fumigatus and fluconazole-resistant C.alb. strains, which is superior or comparable to the activity of the reference drugs fluconazole and voriconazole. Notably, the compounds 23g and 23h exhibited low inhibition profiles for various isoforms of human cytochrome P450 and excellent blood plasma stability., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Fungal infections have became a serious medical problem due to their high incidence and mortality. We describe the discovery and structure-activity relationships studies (SARs) of a series of novel biphenyl imidazole derivatives with excellent antifungal activities against Candida albicans and Cryptococcus neoformans. The most promising compounds 12f-g and 19a-b exhibited excellent activity with minimum inhibitory concentration (MIC) values in the range of 0.03125-2μg/mL. Preliminary mechanism studies showed that the potent antifungal activity of compound 12g stemed from inhibition of CYP51 in Candida albicans. Furthermore, compounds 12g and 19b exhibited low inhibition profiles for various human cytochrome P450 isoforms. The SARs and binding mode established in this study will be useful for further lead optimization., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A series of compounds with benzothiazole and amide-imidazole scaffolds were designed and synthesized to combat the increasing incidence of drug-resistant fungal infections. The antifungal activity of these compounds was evaluated in vitro, and their structure-activity relationships (SARs) were evaluated. The synthesized compounds showed excellent inhibitory activity against Candida albicans and Cryptococcus neoformans. The most potent compounds 14o, 14p, and 14r exhibited potent activity, with minimum inhibitory concentration (MIC) values in the range of 0.125-2 μg/mL. Preliminary mechanism studies revealed that the compound 14p might act by inhibiting the CYP51 of Candida albicans. The SARs and binding mode established in this study are useful for further lead optimization., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)