Visible-Light-Induced Tandem Reaction of Allenes with Selenesulfonates Leading to (E)-2,3-Disulfonylpropene Derivatives.

A visible-light-induced tandem reaction of allenes with selenesulfonates was developed, providing (E)-2,3-disulfonylpropene derivatives in moderate to good yields. This reaction was featured with simple operation, good regioselectivity and stereoselectivity, and wide functional group tolerance. Photoinduced radical additions via energy transfer were proposed.

A metal-free radical cascade reaction of phosphine oxides with 2-aryloxy phenylacetylenes to synthesize diphosphonyl xanthene derivatives.

A radical cascade reaction of 2-aryloxy phenylacetylenes with phosphine oxides promoted by K2S2O8 was developed, which provided diphosphonyl xanthenes as products. This reaction proceeds under transition metal-free and mild conditions with simple operation and good yields. The mechanistic study indicated that phosphine oxide was induced into a phosphonyl radical, and then the following double radical addition/cyclization with 2-aryloxy phenylacetylenes generated bisphosphonyl xanthenes.

Design, Synthesis and Pharmacological Evaluation of Three Novel Dehydroabietyl Piperazine Dithiocarbamate Ruthenium (II) Polypyridyl Complexes as Potential Antitumor Agents: DNA Damage, Cell Cycle Arrest and Apoptosis Induction.

The use of cisplatin is severely limited by its toxic side-effects, which has spurred chemists to employ different strategies in the development of new metal-based anticancer agents. Here, three novel dehydroabietyl piperazine dithiocarbamate ruthenium (II) polypyridyl complexes (6a-6c) were synthesized as antitumor agents. Compounds 6a and 6c exhibited better in vitro antiproliferative activity against seven tumor cell lines than cisplatin, they displayed no evident resistance in the cisplatin-resistant cell line A549/DPP. Importantly, 6a effectively inhibited tumor growth in the T-24 xenograft mouse model in comparison with cisplatin. Gel electrophoresis assay indicated that DNA was the potential targets of 6a and 6c, and the upregulation of p-H2AX confirmed this result. Cell cycle arrest studies demonstrated that 6a and 6c arrested the cell cycle at G1 phase, accompanied by the upregulation of the expression levels of the antioncogene p27 and the down-regulation of the expression levels of cyclin E. In addition, 6a and 6c caused the apoptosis of tumor cells along with the upregulation of the expression of Bax, caspase-9, cytochrome c, intracellular Ca2+ release, reactive oxygen species (ROS) generation and the downregulation of Bcl-2. These mechanistic study results suggested that 6a and 6c exerted their antitumor activity by inducing DNA damage, and consequently causing G1 stage arrest and the induction of apoptosis.

Synthesis and Antiproliferative Evaluation of Novel Hybrids of Dehydroabietic Acid Bearing 1,2,3-Triazole Moiety.

To discover novel potent cytotoxic diterpenoids, a series of hybrids of dehydroabietic acid containing 1,2,3-triazole moiety were designed and synthesized. The target compounds were characterized by means of FT-IR, 1H NMR, 13C NMR, ESI-MS and elemental analysis techniques. The in vitro cytotoxicity of these compounds was evaluated by standard MTT (methyl thiazolytetrazolium) assay against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), BEL-7402 (liver) human carcinoma cell lines and human normal liver cell (HL-7702). The screening results revealed that most of the hybrids showed significantly improved cytotoxicity over parent compound DHAA. Among them, [1-(3-fluorobenzyl)-1H-1,2,3-triazole-4-yl]dehydroabietic acid methyl ester (3c), and [1-(2-nitrobenzyl)-1H-1,2,3-triazole-4-yl]dehydroabietic acid methyl ester (3k) displayed better antiproliferative activity with IC50 (50% inhibitory concentration) values of 5.90 ± 0.41 and 6.25 ± 0.37 µM toward HepG2 cells compared to cisplatin, while they exhibited lower cytotoxicity against HL-7702. Therefore, the 1,2,3-triazole-hybrids could be a promising strategy for the synthesis of antitumor diterpenoids and it also proved the essential role of 1,2,3-triazole moiety of DHAA in the biological activity.

Synthesis and Biological Evaluation of Novel Dehydroabietic Acid-Oxazolidinone Hybrids for Antitumor Properties.

Novel representatives of the important group of biologically-active, dehydroabietic acid-bearing oxazolidinone moiety were synthesized to explore more efficacious and less toxic antitumor agents. Structures of all the newly target molecules were confirmed by IR, ¹H-NMR, 13C-NMR, and HR-MS. The inhibitory activities of these compounds against different human cancer cell lines (MGC-803, CNE-2, SK-OV-3, NCI-H460) and human normal liver cell line LO2 were evaluated and compared with the commercial anticancer drug cisplatin, using standard MTT (methyl thiazolytetrazolium) assay in vitro. The pharmacological screening results revealed that most of the hybrids showed significantly improved antiproliferative activities over dehydroabietic acid and that some displayed better inhibitory activities compared to cisplatin. In particular, compound 4j exhibited promising cytotoxicity with IC50 values ranging from 3.82 to 17.76 µM against all the test cell lines and displayed very weak cytotoxicity (IC50 > 100 µM) on normal cells, showing good selectivity between normal and malignant cells. Furthermore, the action mechanism of the representative compound 4j was preliminarily investigated by Annexin-V/PI dual staining, Hoechst 33258 staining, which indicated that the compound can induce cell apoptosis in MGC-803 cells in a dose-dependent manner and arrest the cell cycle in G1 phase. Therefore, 4j may be further exploited as a novel pharmacophore model for the development of anticancer agents.

A sensitive fluorescence method for detection of E. Coli using rhodamine 6G dyeing.

Negatively charged bacteria combined with positively charged alkaline dye rhodamine 6G (Rh6G) in NaH2 PO4 -Na2 HPO4 buffer solution pH 7.4, by electrostatic interaction. The dyed bacteria exhibited a strong fluorescence peak at 552 nm and fluorescence intensity was directly linear to Escherichia coli (E. coli), Bacillus subtilis (B. subtilis) and Staphylococcus aureus (S. aureus) concentrations in the range of 7.06 × 10(4) to 3.53 × 10(7) , 4.95 × 10(5) to 2.475 × 10(8) and 32.5 to 16250 colony forming unit/mL (cfu/mL) respectively, with detection limits of 3.2 × 10(4) cfu/mL E. coli, 2.3 × 10(5) cfu/mL B. subtilis and 16 cfu/mL S. aureus, respectively. Samples were cultured for 12 h, after which the linear detection range for E. coli was 2 to 88 cfu/mL. This simple, rapid and sensitive method was used for the analysis of water and drinking samples. Copyright © 2015 John Wiley & Sons, Ltd.

A nanogold resonance Rayleigh scattering method for determination of trace As based on the hydride nanoreaction.

In H2 SO4 solution, As(III) was reduced to arsine (AsH3 ) by NaBH4 , and was absorbed in HAuCl4 solution to form nanogold particles (NGs) that exhibited a resonance Rayleigh scattering (RRS) effect at 370 nm. Under the selected conditions, when the As(III) concentration increased the RRS peak also increased due to the formation of more NGs. There was a linear correlation between RRS intensity and As(III) concentration in the range 6-1000 ng/mL, with a detection limit of 3 ng/mL. This new hydride generation-nanogold reaction RRS (HG-NG RRS) method was applied to determine trace amounts of As in milk samples, with satisfactory results.

Causal Associations of PM2.5 and GDM: A Two-Sample Mendelian Randomization Study.

Epidemiological studies have linked particulate matter (PM2.5) to gestational diabetes mellitus (GDM). However, the causality of this association has not been established; Mendelian randomization was carried out using summary data from genome-wide association studies (GWAS). For the analysis of the causal relationship between PM2.5 and GDM, the inverse variance weighted (IVW) method was used. The exposure data came from a GWAS dataset of IEU analysis of the United Kingdom Biobank phenotypes consisting of 423,796 European participants. The FinnGen consortium provided the GDM data, which included 6033 cases and 123,000 controls. We also performed multivariate MR (MVMR), adjusting for body mass index (BMI) and smoking. As a result, we found that each standard deviation increase in PM2.5 is associated with a 73.6% increase in the risk of GDM (OR: 1.736; 95%CI: 1.226-2.457). Multivariable MR analysis showed that the effect of PM2.5 on GDM remained after accounting for BMI and smoking. Our results demonstrate a causal relationship between PM2.5 and GDM.

Aptamer SERS and RRS determination of trace lead ions using nitrogen-doped carbon dot to catalyze the new nano-gold reaction.

Nitrogen-doped carbon dots (CDN) were prepared by microwave hydrothermal method using ammonium citrate (AC) and ethylenediaminetetraacetic acid (EDTA) as precursor. It was characterized by transmission electron microscopy (TEM) and infrared spectroscopy (IR). The CDN was found to catalyze the reduction of HAuCl4 to produce gold nanoparticles (AuNP), among which fructose was an effective reducing agent. Using malachite green (MG) as a molecular probe, the surface enhanced Raman scattering (SERS) intensity at 1617 cm-1 and the resonance Rayleigh scattering (RRS) intensity at 375 nm increased linearly with increasing CDN concentration, respectively. The catalytic activity of CDN is inhibited because the aptamer (Apt) can be adsorbed on the surface of the catalyst CDN. The aptamer (Apt)-Pb2+ reaction and CDN-Apt adsorbing reaction were competitive reaction. When there is Pb2+ that binds more tightly to Apt, Apt is desorbed, and the catalytic ability of CDN is restored. Accordingly, an Apt-mediated nanocatalytic amplification SERS/RRS platform for quantitative detection of lead ions was constructed. For the SERS method, the linear range was 0.5-120 nmol/L with DL of 0.11 nmol/L. For the RRS method, the Pb2+ concentration was linear in the range of 50-400 nmol/L with the RRS intensity, and the DL was 15.32 nmol/L. The analysis platform uses CDN catalyzed nanoreactions to generate AuNP products with SERS activity as a substrate, thus overcoming the shortcomings of Pb2+ without scattering activity, and realizing the possibility of SERS and RRS detection of metal ions. It was used for the determination of Pb2+ in real samples with relative standard deviations were 0.94-2.71 % and recovery was 99.00-103.70 %, respectively. In addition, the mechanism of CDN nanoenzyme heterogeneous catalysis of nano-gold reactions was discussed.

Synthesis and anti-proliferative activity of dehydroabietinol derivatives bearing a triazole moiety.

In search of more efficacious antitumor agents, a series of novel dehydroabietinol derivatives containing a triazole moiety was synthesized, and evaluated for cytotoxicity against four human cancer cell lines. Many exhibited superior cytotoxic profiles compared to the parent molecule, dehydroabietic acid. In particular, compounds 5g, 5i and 5j exhibited promising cytotoxicity with IC50 values ranging from 4.84 to 9.62 µM against all the test cell lines. Cell clone formation and migration tests of compound 5g showed that it not only effectively inhibited the formation of MGC-803 cell colonies but also inhibited the MGC-803 cell migration and invasion. Additionally, the preliminary pharmacological mechanism indicated compound 5g induced apoptosis, arrested the mitotic process at the G0/G1 phase of the cell cycle, reduced the mitochondrial membrane potential, and increased the intracellular ROS and Ca2+ levels.

Discovery of novel sulfonamide chromone-oxime derivatives as potent indoleamine 2,3-dioxygenase 1 inhibitors.

A series of chromone-oxime derivatives containing piperazine sulfonamide moieties were designed, synthesized and evaluated for their inhibitory activities against IDO1. These compounds displayed moderate to good inhibitory activity against IDO1 with IC50 values in low micromolar range. Among them, compound 10m bound effectively to IDO1 with good inhibitory activities (hIDO1 IC50 = 0.64 µM, HeLa IDO1 IC50 = 1.04 µM) and were selected for further investigation. Surface plasmon resonance analysis confirmed the direct interaction between compound 10m and IDO1 protein. Molecular docking study of the most active compound 10m revealed key interactions between 10m and IDO1 in which the chromone-oxime moiety coordinated to the heme iron and formed several hydrogen bonds with the porphyrin ring of heme and ALA264, consistent with the observation by UV-visible spectra that 10m induced a Soret peak shift from 403 to 421 nm. Moreover, compound 10m exhibited no cytotoxicity at its effective concentration in MTT assay. Consistently, in vivo assays results demonstrated that 10m displayed potent antitumor activity with low toxicity in CT26 tumor-bearing Balb/c mice, in comparison with 1-methyl-l-tryptophan (1-MT) and 4-amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide (IDO5L). In brief, the results suggested that chromone-oxime derivatives containing sulfonamide moieties might serve as IDO1 inhibitors for the development of new antitumor agents.

A new and sensitive catalytic resonance scattering spectral assay for the detection of laccase using guaiacol as substrate.

In pH 4.0 succinic acid-sodium hydroxide buffer solution, laccase catalyzed the oxidization of guaiacol substrate to form red particles, which exhibited a strong resonance scattering (RS) peak at 590 nm. Under the chosen conditions, as the laccase increased, the RS intensity (ΔI) increased linearly. The ΔI was proportional to laccase activity in the range of 0.10-1.2 U/mL, with a regression equation of ΔI = 734.0 U(laccase) - 9.7, and a detection limit of 0.05 U/mL. This RS method was applied to the detection of laccase activity in real samples, and the results were agreement with those from spectrophotometry.

A new atomic absorption spectral assay for the determination of trace IgG using immunonanogold.

Nanogold in size of 10 nm was used to label goat anti-human IgG (GIgG) to obtain an immunonanogold probe (AuGIgG) for IgG. In pH 6.8 phosphate buffer solution and in the presence of immunoprecipitator polyethylene glycol 6000 (PEG 6000), IgG reacted with the probe (AuGIgG) to form AuGIgG-IgG-PEG immunocomplex. After the centrifugation to remove the immunocomplex, AuGIgG in the supernatant can be measured by atomic absorption spectrophotometry at gold absorption line 242.8 nm. The results showed that the absorption value decreased as the concentration of IgG increased, and the decreased absorption value was linear to IgG concentration in the range 0.025-0.375 µg/mL, with a detection limit of 0.008 µg/mL. On this base, a new nanogold-labeled atomic absorption spectral assay for IgG was established. The assay was applied to determine IgG in human serum sample with satisfactory results.

Highly selective resonance scattering detection of trace thrombin using aptamer-modified AuRe nanoprobe.

The gold-rhenium (AuRe) composite nanoparticle was prepared by NaBH(4) reduction procedure, and was modified by the aptamer to obtain an AuRe nanoprobe (AuRessDNA) for thrombin. In pH 7.0 Tris-HCl buffer solution and in the presence of salt, the nanoprobe specifically combined with thrombin to form AuRe-aptamer-thrombin cluster that resulted in the resonance scattering intensity (I (560 nm)) increasing at 560 nm. The increased intensity ΔI (560 nm) was linear to the thrombin concentration in the range of 0.115-6.93 nmol/L, with a regression equation of ΔI (560 nm) = 53.0 C + 2.5, a correlation coefficient of 0.9989, and a detection limit of 13 pmol/L. This method was applied to detect thrombin in human plasma samples, with satisfactory results.

SERS spectral study of HAuCl4-cysteine nanocatalytic reaction and its application for detection of heparin sodium with label-free VB4r molecular probe.

In the presence of nanocatalyst, L-cysteine reduce HAuCl4 rapidly to form gold nanoparticles (AuNP), and a quick nanocatalytic preparation procedure was established for Au/AuNP sol with highly active surface enhanced Raman scattering (SERS) effect and good stability. The nanoreaction was also studied by absorption, resonance Rayleigh scattering (RRS), transmission electron microscopy (TEM) and energy spectra. In the selected conditions, the analyte heparin sodium (HS) could react with victoria blue 4 R (VB4r) to form associated complexes which have very weak SERS effect to make the SERS signals decrease. The SERS signals at 1617 cm-1 reduced linearly with HS concentration increasing. Upon addition of FeCl3, it hydrolyzed to form stable Fe(OH)3 sol platform that carried SERS active Au/AuNPs to enhance the sensitivity. Accordingly, we established a SERS quantitative analysis method in the sol substrate of Fe(OH)3-Au/AuNPs, with a linear range of 0.5-75 ng/mL HS and a detection limit of 0.2 ng/mL. HS in real samples was determined, with a relative standard deviation of 2.65-7.63% and a recovery of 99.3-101%.

A stable and reproducible nanosilver-aggregation-4-mercaptopyridine surface-enhanced Raman scattering probe for rapid determination of trace Hg2+.

A stable nanosilver solution was prepared, using PEG10000 as stabilizer and NaBH(4) as reducer. In pH 6.6 Na(2)HPO(4)-NaH(2)PO(4) buffer solution containing PEG10000 and NaCl, the nanosilvers (AgNPs) were aggregated to form the stable nanosilver-aggregation (AgNPA) that could conjugate with 4-mercaptopyridine (MPy) to obtain an AgNPA-MPy surface-enhanced Raman scattering (SERS) probe with a strong SERS peak at 1097 cm(-1). When Hg(2+) concentration increased, the SERS intensity at 1097 cm(-1) decreased linearly as the stable complex of [Hg(MPy)(2)](2+) was formed and the AgNPA particles precipitate to the bottom. The decreased SERS intensity was linear to Hg(2+) concentration in the range of 50-3000 nmol/L. Based on this, a new sensitive SERS method has been proposed for the determination of trace Hg(2+) in the water sample, with satisfactory results.

A highly selective nanogold-aptamer catalytic resonance scattering spectral assay for trace Hg(2+) using HAuCl(4)-ascorbic acid as indicator reaction.

Single strand DNA (ssDNA) was used to modify nanogold to obtain a nanogold-aptamer resonance scattering (RS) probe (NGssDNA) for Hg(2+), based on the formation of stable thymine-Hg(2+)-thymine (T-Hg(2+)-T) mismatches and aggregation of the released nanogold particles. After removing the aggregated particles by filtrate membrane, the excess NGssDNA in the filtration solution exhibit catalytic effect on the gold particle reaction between HAuCl(4) and ascorbic acid (AA) that appear as RS peak at 596nm. When Hg(2+) concentration increased, the RS intensity at 596nm decreased. The decreased intensity is linear to Hg(2+) concentration in the range of 0.00008-0.888ng/mL Hg(2+), with detection limit of 0.000034ng/mL. The nanogold-aptamer catalytic RS assay was applied to determination of Hg(2+) in water with satisfactory results.