Discovery of a polysubstituted phenyl containing novel N-phenylpyrazole scaffold as potent ryanodine receptor activator.

To develop the novel ryanodine receptors (RyRs) insecticides, encouraged by our previous research work, a series of novel N-phenylpyrazole derivatives containing a polysubstituted phenyl ring scaffold were designed and synthesized. The bioassays results indicated that some title compounds exhibited excellent insecticidal activity. For oriental armyworm (Mythimna separata), compounds 7f, 7g, 7i and 7o at 0.5 mg L-1 displayed 100% larvicidal activity, and even at 0.1 mg L-1, 7o was 30% larvicidal activity, comparable to chlorantraniliprole (30%) and better than cyantraniliprole (10%). Compounds 7f and 7o had the median lethal concentrations (LC50) of 8.83 × 10-2 and 7.12 × 10-2 mg L-1, respectively, close to chlorantraniliprole (6.79 × 10-2 mg L-1). Additionally, for diamondback moth (Plutella xylostella), the larvicidal activity of compounds 7f and 7i were 90% and 70% at 0.01 mg L-1, respectively, better than chlorantraniliprole (50%) and cyantraniliprole (40%). More impressively, the LC50 value of 7f was 4.2 × 10-3 mg L-1, slightly lower than that of chlorantraniliprole (5.0 × 10-3 mg L-1). The molecular docking between compound 7f and RyRs of diamondback moth validated our molecular designation. Furthermore, the calcium imaging experiment explored the influence of compound 7o on the calcium homeostasis in the central neurons of the third larvae of oriental armyworm. The results of this study indicated that 7o is a potent novel lead targeting at RyRs.

Effects of coordination and manipulation therapy for patients with Parkinson disease.

PURPOSE: To determine the effects of a new exercise training regimen, i.e. coordination and manipulation therapy (CMT), on motor, balance, and cardiac functions in patients with Parkinson disease (PD). MATERIALS AND METHODS: We divided 36 PD patients into the CMT (n = 22) and control (n = 14) groups. The patients in the CMT group performed dry-land swimming (imitation of the breaststroke) and paraspinal muscle stretching for 30 min/workday for 1 year. The control subjects did not exercise regularly. The same medication regimen was maintained in both groups during the study. Clinical characteristics, Unified Parkinson's Disease Rating Scale (UPDRS) scores, Berg balance scale (BBS) scores, mechanical balance measurements, timed up and go (TUG) test, and left ventricular ejection fraction (LVEF) were compared at 0 (baseline), 6, and 12 months. Biochemical test results were compared at 0 and 12 months. The primary outcome was motor ability. The secondary outcome was cardiac function. RESULTS: In the CMT group, UPDRS scores significantly improved, TUG test time and step number significantly decreased, BBS scores significantly increased, and most mechanical balance measurements significantly improved after 1 year of regular exercise therapy (all p < 0.05). In the control group, UPDRS scores significantly deteriorated, TUG test time and step number significantly increased, BBS scores significantly decreased, and most mechanical balance measurements significantly worsened after 1 year (all P < 0.05). LVEF improved in the CMT group only (P = 0.01). CONCLUSIONS: This preliminary study suggests that CMT effectively improved mobility disorder, balance, and cardiac function in PD patients over a 1-year period.

[Screening based on response surface methodology of multi-fractions traditional Chinese medicine with anti-influenza virus neuraminidase activity: take shuanghuanglian injection as an example].

This study aimed to establish a novel method to screen out the combined components of multi-fractions traditional Chinese medicine (TCM), so that the internal relationship between multi-ingredients could be objectively assessed and the proportioning ratio could be optimized. Taking antiviral effect on neuraminidase activity of influenza virus as the evaluating indicator and using Box-Behnken response surface methodology, the main effective ingredients of Shuanghuanglian injection (SHL) were screened. Meanwhile, the relationship between active ingredients was discussed. Taking SHL as a comparison, the optimum proportioning ratio was predicted. The results indicated that chlorogenic acid, cryptochlorogenic acid, caffeic acid and baicalin have comparatively strong antiviral activity against influenza virus. Moreover, antagonistic action existed between chlorogenic acid and cryptochlorogenic acid, whereas synergistic action between caffeic acid and other components. The optimum proportioning ratio resulted from fitted model is: chlorogenic acid, cryptochlorogenic acid, caffeic acid and baicalin (107 microg x mL(-1) : 279 microg x mL(-1) : 7.99 microg x mL(-1) : 92 microg x mL(-1)). The antiviral activity of the recombined components is stronger than that of SHL, which was consistent with the experiment results (P < 0.05). Box-Behnken response surface methodology has the advantages of general-screening, high-performance and accurate-prediction etc, which is appropriate for screening the combined components of multi-fractions TCM and the optimization of the proportioning ratio. The proposed method can serve as a technological support for the development of modern multi-fractions TCM.

Antifungal activities of triterpenoids from the roots of Astilbe myriantha Diels.

During a search for plant extracts that possess activity against the fungi that cause diseases in plants, a 95% ethanol extract from the roots of Astilbe myriantha Diels showed inhibitory activity against Colletotrichum gloeosporioides. Bioassay-guided fractionation of the 95% ethanol extract led to the isolation of seven triterpenoids (1-7). Their structures were elucidated by spectroscopy and by a comparison with literature data. Among these compounds, 3ß,6ß,24-trihydroxyurs-12-en-27-oic acid (7) was the most active inhibitor of C. gloeosporioides, with >68.0% inhibition at 100mg/ml after 72h. Moreover, compound 7 displayed broad-spectrum inhibitory activity against Rhizoctonia solani, Fusarium oxysporum f. sp. Niveum, Fusarium oxysporum f. sp. Cubens, C. gloeosporioides, Penicillium citrinum, Colletotrichum lagenarium, and Penicillium digitatum, with EC50 values ranging from 13.9 to 34.0µg/ml. The potential of compound 7 as a fungicide is therefore promising. In addition, compound 1 was found to be a new triterpenoid, 3ß,6ß-dihydroxyurs-12-en-7α,27α-olide, which possesses six rings.

Design, synthesis and biological activity of new strobilurin derivatives with a 1H-pyrazol-5-oxy side chain.

A series of new strobilurin derivatives with a substituted pyrazole side chain (5 and 6) were designed and synthesized. The new derivatives were synthesized from substituted phenones as starting material via esterification, cyclization and condensation reactions. All compounds were identified by 1H NMR and IR spectral and elemental analyses. Preliminary biological evaluation showed that some of the compounds had good fungicidal activity against cucumber downy mildew (CDM) and wheat powdery mildew (WPM) at 6.25 and 1.56 mg L(-1), respectively. Some of the compounds showed insecticidal activity against armyworm (AW), green peach aphid (GPA) and culex mosquitoes at 600 mg L(-1).

Vladimuliecins A and B: cytotoxic pentacyclic pregnanols from Vladimiria muliensis.

Two new steroids, vladimuliecins A (1) and B (2), were isolated by bioassay-guided fractionation from the rhizome of Vladimiria muliensis. Compounds 1 and 2 are the first examples possessing a pentacyclic 3alpha,5alpha-cyclopregnane-type framework. The structures of vladimuliecins A (1) and B (2) and their deacetylated derivative (3) were determined on the basis of IR, MS, 1D NMR, 2D NMR, and X-ray data analyses. The absolute configuration of the 10 stereogenic centers of compounds 1 and 2 was determined to be 3R,5R,6R,8S,9R,10R,13R,14R,17S,20R by means of auxiliary chiral MTPA derivatives and optical rotation calculation. A probable biosynthesis pathway to 1 and 2 is also proposed and discussed. In addition, the cytotoxicity of compounds 1, 2, and 3 was evaluated against selected cancer cell lines, including human leukemia cell (HL-60), human hepatoma cell (SMMC-7721), and human cervical carcinoma cell (HeLa) lines.

The role of N-lauroylethanolamine in the regulation of senescence of cut carnations (Dianthus caryophyllus).

N-acylethanolamines (NAEs) are a group of lipid mediators that play important roles in mammals, but not much is known about their precise function in plants. In this work, we analyzed the possible involvement of N-lauroylethanolamine [NAE(12:0)] in the regulation of cut-flower senescence. In cut carnation flowers of cv. Red Barbara, the pulse treatment with 5 microM NAE(12:0) slowed senescence by delaying the onset of initial wilting. Ion leakage, which is a reliable indicator of membrane integrity, was postponed in NAE(12:0)-treated flowers. The lipid peroxidation increased in carnation petals with time, in parallel to the development in activity of lipoxygenase and superoxide anion production rate, and these increases were both delayed by NAE(12:0) supplementation. The activities of four enzymes (superoxide dismutase, catalase, glutathione reductase and ascorbate peroxidase) that are implicated in antioxidant defense were also upregulated in the cut carnations that had been treated with NAE(12:0). These data indicate that NAE(12:0)-induced delays in cut-carnation senescence involve the protection of the integrity of membranes via suppressing oxidative damage and enhancing antioxidant defense. We propose that the stage from the end of blooming to the onset of wilting is a critical period for NAE(12:0) action.