Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1.

The natural product, rutaecarpine (RUT), is the main effective component of Evodia rutaecarpa which is a widely used traditional Chinese medicine. It has vasodilation, anticoagulation, and anti-inflammatory activities. However, further therapeutic applications are limited by its cytotoxicity. Thus, a derivative of RUT, 10-fluoro-2-methoxyrutaecarpine (F-RUT), was designed and synthesized that showed no cytotoxicity toward RAW264.7 macrophages at 20 µM. In an anti-inflammation experiment, it inhibited the production of nitric oxide (NO) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages; cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) induced by LPS were also downregulated. After 24 h of treatment, F-RUT significantly inhibited cell migration and invasion of ovarian A2780 cells. Furthermore, F-RUT promoted expressions of transient receptor potential vanilloid type 1 (TRPV1) and endothelial (e)NOS in human aortic endothelial cells, and predominantly reduced the inflammation in ovalbumin/alum-challenged mice. These results suggest that the novel synthetic F-RUT exerts activities against inflammation and vasodilation, while displaying less toxicity than its lead compound.

Design and synthesis of ultrasensitive off-on fluoride detecting fluorescence probe via autoinductive signal amplification.

We prepared an off-on fluorometric probe, DPF1, by incorporating the concept of autoinductive signal amplification into its molecular design. In the presence of fluoride, DPF1 undergoes a cascade of self-immolative reactions concomitant with unmasking fluorogenic coumarin, which results in the ejection of two fluoride ions. These fluoride ions are continuously activating the cascade reaction and accumulating coumarins, which leads to exponentially amplifying the signal with high sensitivity. The fluorescence signal generated by this cascade reaction is rapid, specific and insensitive to other anions. Its limit of detection was 0.5 pM, considerably lower than other current methods of fluoride detection. In addition, DCC, a long wavelength fluorometric probe, was prepared. Interestingly, an assay platform coupling DPF1 and DCC showed an outstanding sensing ability at higher wavelengths, suggesting that this can be a promising method for the sensitive and selective detection of fluoride in biological samples. The practical applicability of the proposed approach has been demonstrated in urine and water samples.

Electrochemical OFF-ON ratiometric chemodosimeters for the selective and rapid detection of fluoride.

We have described two "OFF-ON electrochemical latent ratiometric redox chemodosimeters", 1,4-Bis(tert-butyldimethylsiloxy)benzene (H2Q') and 1,4-Bis (tert-butyldimet hylsiloxy)-2-methoxybenzene (MH2Q') for the selective detection of inorganic fluoride. The electrochemical signals of hydroquinone (H2Q) and o-methoxy hydroquinone (MH2Q) within this latent redox probes (H2Q' and MH2Q') were completely masked by protecting their hydroxyl group as silylether (OFF state). The externally added fluoride ions triggered the deprotection of H2Q' and MH2Q' and unmasked the electrochemical properties of H2Q and MH2Q respectively. The electrochemical reporters (H2Q and MH2Q) presented a pair of redox peaks at the electrode surface (ON state) and the peak currents are linearly dependent with the concentration of fluoride which leading to the ratiometric detection of fluoride. The limit of detection (signal-to-noise ratio=3) observed for the probes are 23.8 µM and 2.38 µM for H2Q' and MH2Q' respectively. The deprotection is highly selective for fluoride over other anions investigated. The probes are highly stable and the proposed approach offers rapid response time and promising practical applicability. The proposed strategy holds great promise for the commencement of new H2Q based electrochemical probes by tuning the electrochemical behavior of H2Q.

Low-cytotoxic synthetic bromorutaecarpine exhibits anti-inflammation and activation of transient receptor potential vanilloid type 1 activities.

Rutaecarpine (RUT), the major bioactive ingredient isolated from the Chinese herb Evodia rutaecarpa, possesses a wide spectrum of biological activities, including anti-inflammation and preventing cardiovascular diseases. However, its high cytotoxicity hampers pharmaceutical development. We designed and synthesized a derivative of RUT, bromo-dimethoxyrutaecarpine (Br-RUT), which showed no cytotoxicity at 20 µM. Br-RUT suppressed nitric oxide (NO) production and tumor necrosis factor-α release in concentration-dependent (0~20 µM) manners in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages; protein levels of inducible NO synthase (iNOS) and cyclooxygenase-2 induced by LPS were downregulated. Br-RUT inhibited cell migration and invasion of ovarian carcinoma A2780 cells with 0~48 h of treatment. Furthermore, Br-RUT enhanced the expression of transient receptor potential vanilloid type 1 and activated endothelial NOS in human aortic endothelial cells. These results suggest that the synthetic Br-RUT possesses very low cytotoxicity but retains its activities against inflammation and vasodilation that could be beneficial for cardiovascular disease therapeutics.

Vapor-based synthesis of maleimide-functionalized coating for biointerface engineering.

Chemical vapor deposition polymerization was used to deposit a novel maleimide-functionalized poly-p-xylylene coating on various substrates. The coated substrates are readily able to undergo thiol-maleimide click reaction under mild conditions. Applications using this coating technology are highlighted in low-protein-fouling modification as well as manipulated attachments and growth of bovine arterial endothelial cells.