Extracts of Lycoris aurea induce apoptosis in murine sarcoma S180 cells

Lycoris species have been known since long ago as a multi-utility ethnomedicinal herbal in China. It has been reported to exhibit a number of properties such as anticancer, neuroprotective, and antibacterial activities. In the present study, the anticancer efficacy of dichloromethane extracts of Lycoris aurea (DELA), was evaluated both in vivo and in vitro using murine sarcoma 180 cells. To evaluate the effects of DELA on apoptotic cell death, flow cytometry and Western blotting were performed. DELA demonstrated promising inhibition effects on sarcoma 180 cells in vitro and a 53.49% inhibitory rate on cancer cells in vivo. DELA treatment increased thymus indices and spleen indices in vivo, indicating that it reduced tumours, but did not damage the main immune organs. The DELA-evoked increase in apoptotic cell death was accompanied by occurrence of cleaved caspase-3 and decreases in the ratio of Bcl-2/Bax. Further purification and LCMS analysis showed DELA contained homolycorine, 2α-hydroxyoduline, oduline, hippeastrine, 2α-hydroxy-6-O- methyloduline, and 2α-methoxy-6-O-methyloduline. These results indicate that DELA exerted its anticancer effects, at least in part, by inducing cancer cell apoptosis and thus can be considered as a potential candidate agent for treatment of cancer.     

Parallel synthesis of 2-substituted 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidine-5-carboxamides

A library of 24 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidine-5-carboxamides 10{1,2; 1-12} was prepared by a parallel solution-phase approach. The synthesis comprises a five-step transformation of itaconic acid (11) into 1-methyl and 1-phenyl substituted 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidine-5-carboxylic acids 17{1,2} followed by parallel amidation of 17{1,2} with a series of 12 aliphatic amines 18{1-12} to afford the corresponding carboxamides 10 in good overall yields and in 80-100% purity.     

p-Cymene protects mice against lipopolysaccharide-induced acute lung injury by inhibiting inflammatory cell activation

The objective of this study was to test the hypothesis that p-cymene can attenuate acute lung injury induced by lipopolysaccharide (LPS) in vivo. In the mouse model of LPS-induced acute lung injury, intraperitoneal preconditioning with p-cymene resulted in a significant reduction of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), lung water gain, inflammatory cell infiltration, lung tissue myeloperoxidase activity. In addition, p-cymene blocked the phosphorylation of IκBα protein and mitogen-activated protein kinases (MAPK) signaling pathway activation. Histopathologic examination of lung tissue indicated that p-cymene treatment markedly decreased focal thickening, congestion, pulmonary edema, and inflammatory cells infiltration. The results showed that p-cymene had a protective effect on LPS-induced ALI in mice.     

Organotellurium-bridged cyclodextrin dimers as artificial glutathione peroxidase models

To elucidate the importance of the goodness of fit in complexes between substrates and glutathione peroxidise (GPX) mimics, we examined the decomposition of a variety of structurally distinct hydroperoxides at the expense of glutathione (GSH) catalyzed by 2,2′-ditellurobis(2-deoxy-γ-cyclodextrin) (2-Te-γ-CD), and by the corresponding derivatives of β-cyclodextrin (β-CD) and α-cyclodextrin. The good fit of the cumene group into the γ-CD binding cavity reflected the result of well-defined reaction geometry, leading to the most excellent peroxidase activity with high substrate specificity. Furthermore, the catalytic constant and the combination with the best binding also exhibited the highest regioselectivity in the substrate decomposition. Saturation kinetics were observed and the catalytic reaction agreed with a ping-pong mechanism, in analogy with natural GPX, and might exert its thiol peroxidase activity via tellurol, tellurenic acid, and tellurosulfide. The stoichiometry of the inclusion complex was determined to be of 2:1 host-to-guest. The value of stability constant K _c for (2-Te-γ-CD)₂/GSH at room temperature was calculated to be 3.815?×?10⁴?M^?2, which suggested that 2-Te-γ-CD had a moderate ability to bind GSH. Importantly, the proposed mode of the (2-TeCD)₂/GSH complex was the possible important noncovalent interactions between enzymes and substrates in influencing catalysis and binding.     

Enzyme-linked immunosorbent assay and immunochromatographic strip for rapid detection of atrazine in water samples

We have developed a heterologous direct competitive enzyme-linked immunosorbent assay (ELISA) and a colloidal gold-based immunochromatographic (ICG) strip for the determination of the herbicide atrazine in water samples. The ELISA had a half-maximum inhibition concentration (IC₅₀) of 0.12 ng mL^?1 and a limit of detection (LOD, calculated as the IC₁₅ value) of 0.01 ng mL^?1. The average of recoveries for all spiked water samples was 96.5%. There was a good correlation between the data determined by this ELISA and those obtained by high performance liquid chromatography (HPLC) (r ² ?=?0.996). The visual LOD of the ICG strip assay was 2 ng mL^?1. The assay process only took 10 min, and no sample pretreatment was required. Its high specificity, sensitivity and fast detection made the strip well suited for on-site screening of atrazine in water samples. Both the ELISA and the ICG strip assay are useful for rapid analysis of a large number of water samples at low cost.

Synthesis and functionalization of new polyhalogenated BODIPY dyes. Study of their photophysical properties and singlet oxygen generation

A theoretical and experimental study on the iodination of BODIPY dyes with different degrees of substitution has been developed. Polyhalogenated BODIPYs synthesized in this work are the first examples of this type of dyes with more than two halogen atoms in the BODIPY core and they can be selectively functionalized. Surprisingly, the position in which halogen is attached has a marked effect in the photophysical properties and modulates the fluorescence capacity of the resulting BODIPY. These iodinated BODIPYs are efficient singlet oxygen generators.     

Optimal strategies for determination of free/extractable and total microcystins in lake sediment

The optimization of analytical procedures for the quantification of free and total microcystins (MCs) in natural sediments was systematically examined based on solvent extraction and Lemieux oxidation. In this optimized analytical procedure, a sequential solvent extraction using 50% (v/v) methanol and EDTA-sodium pyrophosphate was selected as the optimal extraction solvent for free MCs analysis, after which the purified extracts and sediment residuals were applied to the optimized Lemieux oxidation for determination of total MCs in lake sediments. The optimized procedures were shown to be efficient and reliable for the routine analysis of both free and total MCs in lake sediment samples, as indicated by the minimal adverse impact of sediment organic matter on the recovery of free MCs and yield of MMPB (2-methyl-3-methoxy-4-phenylbutyric acid). Finally, the developed procedures were applied to field sediment samples collected from Lake Dianchi during a bloom season and seven of thirty samples showed positive results.     

Investigation on the oxidation of aryl oxiranylmethanols and the synthesis of 2-aryl-N-thiazolyl-oxirane-2-carboxamides as glucokinase activators

RuCl₃/NaIO₄-initiated oxidation of oxiranemethanols was investigated, and two products, oxirane-2-carboxylic acid and (5′-oxotetrahydrofuran-3-yl)acetic acid, were obtained in variant ratios. The product structures were determined and a tentative mechanism involving oxidation-rearrangement-oxidation process was proposed. Glucokinase enzymatic assay revealed that oxiranecarboxamides 4a-c retained moderate GK activation potency with amide 4a showing an EC₅₀ value of 584 nM and a high activation fold of 3.14. However, (5′-oxotetrahydrofuran-3-yl)acetamide 11a is inactive. This study not only provided an alternative protocol to access (5′-oxotetrahydrofuran-3-yl)acetic acid analogs, but also yielded nanomolar GA activators (esp. 4a) for further structure-activity relationship study.     

Resorcinarene-based cavitands with chiral amino acid substituents for chiral amine recognition

Resorcinarene-based deep cavitands alanine methyl resorcinarene acid (), alanine undecyl resorcinarene acid () and glycine undecyl resorcinarene acid (), which contain chiral amino acids, have been synthesized. The upper rim of the resorcinarene host is elongated with four identical substituents topped with alanine and glycine groups. The structures of the new resorcinarenes were elucidated by nuclear magnetic resonance (NMR), mass spectrometry (MS) and the sustained off-resonance irradiation collision induced dissociation (SORI-CID) technique in FTICR-MS. These studies revealed that eight water molecules associate to the cavitand, two for each alanine group. The alanine substituent groups are proposed to form a kite-like structure around the resorcinarene scaffold. The binding of , , and with chiral R- and S-methyl benzyl amines was studied by (1)H NMR titration, and compared to that of a binary l-tartaric acid and the monoacid phthalyl alanine (). The results show that these compounds interact with amine guests; however, with four carboxylic acid groups, they bind several amine molecules strongly while the binary l-tartaric acid only binds one amine guest strongly. The simple compound , which contains one carboxylic group, shows weak binding to the amines. The (1)H NMR titration of with primary, secondary, and tertiary chiral amines showed that it can discriminate between these three types of amines and showed chiral discrimination for chiral secondary amines.