Photochemical Selective Oxidation of Benzyl Alcohols to Aldehydes or Ketones.

Using Eosin Y as a metal-free photocatalyst and O2 as an oxidant, the present study reports a new photochemical protocol that enables efficient aerobic oxidation of various benzyl alcohols to the corresponding aldehydes or ketones in excellent yields under mild reaction conditions. The catalyst system presents good functional-group tolerance and exquisite chemoselectivity, which also can easily be scaled-up to gram scale. Moreover, the methodological applications in practical synthesis of several organic molecules and the primary reaction mechanism were also discussed.

Multifunctional Fluorescent Probe for Simultaneously Detecting Microviscosity, Micropolarity, and Carboxylesterases and Its Application in Bioimaging.

Based on OR logic gate, we proposed a smart near-infrared (NIR) fluorescent probe, named VPCPP, for simultaneously monitoring local microviscosity, micropolarity, and carboxylesterases (CEs) in living cells through blue and red channels. This proposed probe was capable of distinguishing cancer cells from normal cells and had good potential for identifying living liver cell lines. Furthermore, the fluctuations of the three analytes of interest in different cell status was successfully explored. Particularly, facilitated with high-content analysis (HCA) and VPCPP, a simple and efficient high-throughput screening (HTS) platform was first constructed for screening antitumor drugs and studying their effect on the analytes. For the first time, we found that sorafenib-induced ferroptosis led to an increase in the microviscosity and up-regulation of CEs at the same time. Additionally, the procedure that aristolochic acid (AA) induced the overexpression of CEs was verified. Besides, VPCPP was utilized for imaging the variations of the two microenvironment parameters and CEs in the inflammation model. Finally, VPCPP was able to image the tumor ex vivo and in vivo through two channels and one channel separately, as well as to visualize the kidneys and liver ex vivo with dual emissions, which indicated that the probe had great potential for imaging applications such as medical diagnosis, preclinical research, and imaging-guided surgery.

A novel quinoline-based fluorescent probe for real-time monitoring of Cys in glioma.

Cysteine (Cys), a small-molecule biothiol, has recently been identified as a novel Glioblastoma (GBM) biomarker. The highly selective real-time monitoring and fluorescence imaging of Cys levels in vivo is of great significance for the early diagnosis and treatment of GBM. In this work, we reported a highly selective Cys fluorescent probe ZS-C1, based on quinoline according to the mechanism of the conjugate addition cyclization reaction. The Limit of Detection (LOD) of probe ZS-C1 was 1.97 µM, λex = 380 nm; λem = 531 nm. In vitro experiments showed that ZS-C1 could be distinguished from Hcy and GSH significantly, and the fluorescence quantum yield was reduced by 30 times. Further, biological imaging and 3D tumor sphere penetration assay showed that the ZS-C1 could monitor both exogenous and endogenous Cys in the living U87MG cells, and the fluorescence of probe ZS-C1 diffusely distributed inside the U87MG three-dimensional solid cell spheroid (up to 60 µM deep into the solid tumors). This work provided a potential tool for further investigations of Cys in biological samples and critical information for early diagnosis of glioma and guidance for clinical surgery.

Pd-Catalyzed Direct Diversification of Natural Anti-Alzheimer's Disease Drug: Synthesis and Biological Evaluation of N-Aryl Huperzine A Analogues.

The first systematic direct diversification of a complex natural product by metal-catalyzed N-H functionalization was carried out. A new series of N-(hetero)aryl analogues (1-32) of the natural anti-Alzheimer's disease drug huperzine A (HPA) was prepared via palladium-catalyzed Buchwald-Hartwig cross-coupling reactions of HPA with various aryl bromides in good yields. Most of the N-aryl-huperzine A (N-aryl-HPA) analogues showed good acetylcholinesterase (AChE) inhibitory activity in in vitro experiments. Three arylated huperzine A analogues (14, 19, and 30) exhibited stronger anti-AChE activity than HPA. The 5-methoxy-2-pyridyl analogue (30) displayed the most potent AChE inhibition activity, with an IC50 value of 1.5 µM, which was 7.6-fold more active than HPA. Compound 30 also exhibited better neuroprotective activity for H2O2-induced damage in SH-SY5Y cells than HPA. Structure-activity relationship analysis suggested that the electron density of the installed aromatic ring or heteroaromatic ring played a significant role in inducing the AChE inhibition activity. Overall, compound 30 showed the advantages of easy synthesis, high potency and selectivity, and improved neuroprotection, making it a potential huperzine-type lead compound for Alzheimer's disease drug development.

Developing potential Helicobacter pylori urease inhibitors from novel oxoindoline derivatives: Synthesis, biological evaluation and in silico study.

By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC50 = 0.71 µM; MIC = 0.48 µM) than the positive controls AHA (IC50 = 17.2 µM) and Metronidazole (MIC = 31.3 µM). With low cytotoxicity, it showed considerable potential for further development. Docking simulation revealed the possible binding pattern of this series. 3D QSAR model was built to discuss SAR and give useful hints for future modification.

Late-Stage Modification of Medicine: Pd-Catalyzed Direct Synthesis and Biological Evaluation of N-Aryltacrine Derivatives.

A new series of N-aryltacrine derivatives were designed and synthesized as cholinesterase inhibitors by the late-stage modification of tacrine, using the palladium-catalyzed Buchwald-Hartwig cross-coupling reaction. In vitro inhibition assay against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) demonstrated that most of the synthesized compounds had potent AChE inhibitory activity with negative inhibition of BuChE. Among them, N-(4-(trifluoromethyl)phenyl)-tacrine (3g) and N-(4-methoxypyridin-2-yl)-tacrine (3o) showed the most potent activity against AChE (IC50 values of 1.77 and 1.48 µM, respectively). The anti-AChE activity of 3g and 3o was 3.5 times more than that of tacrine (IC50 value of 5.16 µM). Compound 3o also displayed anti-BuChE activity with an IC50 value of 19.00 µM. Cell-based assays against HepG2 and SH-SY5Y cell lines revealed that 3o had significantly lower hepatotoxicity compared to tacrine, with additional neuroprotective activity against H2O2-induced damage in SH-SY5Y cells. The advantages including synthetic accessibility, high potency, low toxicity, and adjunctive neuroprotective activity make compound 3o a new promising multifunctional candidate for the treatment of Alzheimer's disease.

Pd-Catalyzed Direct Modification of an Anti-Alzheimer's Disease Drug: Synthesis and Biological Evaluation of α-Aryl Donepezil Analogues.

Palladium/BuAd2P efficiently catalyzed the direct α-arylation of ketone in the anti-Alzheimer's disease drug donepezil, leading to 15 aryldonepezil analogues exhibiting high selective inhibition of acetylcholinesterase (AChE). The cell-based assays revealed that the 3-methylpridinyl analogue (12) shows significantly lower toxicity compared to donepezil and remarkable neuroprotective activity against H2O2-induced damage in SH-SY5Y cells. Docking results of compound 12 also interpreted the possible mechanism of the selective inhibition between AChE and butyrylcholinesterase (BuChE).

An Activatable and Switchable Nanoaggregate Probe for Detecting H2 S and Its Application in Mice Brains.

Employing a sequentially activated probe design method, an activatable, switchable and dual-mode probe was designed. This nanoprobe, HSDPP, could be effectively activated by H2 S to form H-type aggregates with green emission; subsequently, the aggregates could bind to mtDNA to form monomers and the emIssion color switched from green to deep-red. We exploited HSDPP to image exogenous and endogenous H2 S in living cells. Of note, for the first time, this novel nanoprobe with an optimal partition coefficient value (LogP=1.269) was successfully applied for tracking the endogenous H2 S upregulation stimulated by cystathionase activator S-adenosyl-L-methionine (SAM) in mice brains. Finally, our work provides an invaluable chemical tool for probing endogenous H2 S upregulation in vitro/vivo and, importantly, affords a prospective design strategy for developing switchable chemosensors to unveil the relationship between biomolecules and DNA in mitochondria in many promising areas.

A new selective fluorescence probe with a quinoxalinone structure (QP-1) for cysteine and its application in live-cell imaging.

A new selective probe with a quinoxalinone structure, QP-1, has been developed for detection of Cys from biothiols. QP-1 features superb selectivity to Cys and a wide pH range. QP-1 has selectivity to Cys over Hcy, GSH, other amino acids and ions. HRMS spectra confirmed that the detection process was a conjugate addition-addition-elimination reaction. Moreover, QP-1 has been successfully applied in the imaging of Cys in living cells. Finally, QP-1 has been used to detect Cys in rat urine samples.

Hypolipidemic activity in Sprague-Dawley rats and constituents of a novel natural vegetable oil from Cornus wilsoniana fruits.

UNLABELLED: Cornus wilsoniana Wanger is a woody oil plant distributed in the south region of the Yellow River, China. Its oil has been taken as edible oil for over 100 y, and consumption of such oil is believed to prevent hyperlipidemia in Chinese folk recipe. This study has investigated the hypolipidemic effect of Cornus wilsoniana oil (CWO) in Sprague-Dawley rats. The results demonstrated that CWO could significantly decrease total cholesterol (TC), total triacylglycerol (TG), and low-density lipoprotein cholesterol (HDL-C) in serum, liver weight, hepatic TC, and TG. After analyzing the chemical constituents of CWO, we found that the content of unsaturated fatty acids (UFA) was very high (69.12%). Specially, the n-6 polyunsaturated fatty acids (PUFA), including linoleic acid, γ-linolenic acid, and 11,14-eicosadienoic acid, accounted very great proportion (38.86%). The high hypolipidemic activity of CWO might be attributed to the lipid-lowering functions of these polyunsaturated fatty acids. Molecular docking was further performed to study the binding model of fatty acids (FA) from CWO to a possible hypolipidemic target, peroxisome proliferator-activated receptor δ (PPARδ). The results showed that linoleic acid and γ-linolenic acid could bind PPARδ very well. PRACTICAL APPLICATION: Cornus wilsoniana oil could be used as equilibrated dietary oil, not only having hypolipidemic function, but also helping to overcome essential fatty acids deficiency.

[Effecive observation of percutaneous reduction and Kirschner pin fixation for treatment of supracondylar fracture of humerus in children].

OBJECTIVE: To study on the clinic effect of percutaneous reduction and Kirschner's pins fixation for treatment of supracondylar fracture of humerus in children. METHODS: From June 2001 to Nov. 2007, 26 patients of supracondylar fracture of humerus in children were reviewed. All patients were treated by the fixation of percutaneous reduction and Kirschner's pins under the C-arm X-ray machine. These patients were included 16 males and 10 females with the age from 3 to 10 years. There were 17 cases on the left and 9 cases on the right. There were 24 cases of extension type and 2 cases of flexing type and all the cases were considered as closed fracture without any injury on nerve and vascular. These patients were all under operation from half an hour to 7 days after being injured, and 15 of them were sent to the hospital and received operation immediately. RESULTS: These 26 cases were followed-up for 3 to 9 months, all fractures of them were healing. According to the comprehensive evaluation, the result of 16 cases were excellent, 8 cases were good, and 2 cases were fine. CONCLUSION: From the research, the method of percutaneous reduction and Kirschner's pins fixation for treatment of supracondylar fracture of humerus in children with the assistance from C-arm X-ray machine is safe, convenient, less injured, with reliable fixation, complication-minimizing, and easy for functional recover.