Castro Wilcox (gametrial48)

Michael, Michael-annulation, and oxa-Diels-Alder reactions of carbohydrate derivatives that afford polyoxy-functionalized piperidine derivatives bearing tetrasubstituted carbon at the 3-position of the piperidine ring are reported. Iminium ions generated from carbohydrate derivatives with amines were converted to enamines in situ, which acted as nucleophiles. As a result, substituents were introduced at the 3-position or both 2- and 3-positions of the piperidines bearing polyoxy groups. This strategy will be useful in drug discovery efforts.Growth from spores activated a biosynthetic gene cluster in Actinomadura sp. RB29, resulting in the identification of two novel groups of halogenated polyketide natural products, named maduralactomycins and actinospirols. The unique tetracyclic and spirocyclic structures were assigned based on a combination of NMR analysis, chemoinformatic calculations, X-ray crystallography, and 13C labeling studies. On the basis of HRMS2 data, genome mining, and gene expression studies, we propose an underlying noncanonical angucycline biosynthesis and extensive post-polyketide synthase (PKS) oxidative modifications.Small-molecular fluorescence sensors have become promising detection tools in many fields attributing to their high sensitivity, excellent temporal and spatial resolution, and low cytotoxicity. However, high concentration or aggregation-induced fluorescence quenching effect has usually hindered the development of traditional fluorescence dyes. Herein, a new fluorophore cyanovinylene dye BMZ with excimer emission property has been constructed. It shows an obvious enhanced and red-shift emission upon aggregation in aqueous solution, which overmatches the conventional pyrene with longer absorption and emission wavelengths. Using this unique optical property, a new fluorescence probe BMZ-Gal has been developed for trapping of β-galactosidase (β-Gal) activity with high selectivity, low limit of detection of 0.17 U, and rapid recognition, which is based on the β-Gal-induced formation of red-shift emitting excimer. β-Gal has a strong affinity for BMZ-Gal, which is verified through the Michaelis-Menten constants (Km, 1.87 μM) and the hydrolysis efficiencies (Kcat/Km, 1.78 × 103 M-1 s-1). Furthermore, the assay system has been successfully used for detecting endogenous β-Gal in living ovarian cancer cells and can passively targeted to identify β-Gal in organelle level and determine its subcellular location with satisfactory accuracy. We anticipate that the new fluorophore cyanovinylene dye herein may inaugurate new opportunities for the development of excimer emission sensors.Eight new nitrogenated azaphilones (1-8) and two known compounds (chaetoviridin A and chaetoviridin E, 9, 10) were isolated from the culture of the deep-sea-derived fungus Chaetomium globosum MP4-S01-7. The absolute configurations of new compounds were elucidated by HSQC-HECADE NMR data, J-based configuration analysis, and modified Mosher's method and finally verified by comparison of recorded and computed NMR chemical shifts from quantum chemical calculations coupled with a statistical procedure (DP4+). All of the compounds were evaluated for their in vitro cytotoxicities against the gastric cancer cell lines MGC803 and AGS, and most of them showed significant inhibition on cancer cell viability at 10 μM. Among them, compounds 1, 2, and 5 exerted the most potent cytotoxic activities, with IC50 values less than 1 μM. Further studies showed that compound 2 inhibited cell cycle progression, and both compounds 1 and 2 induced apoptosis of gastric cancer cells in a concentration-dependent manner.In this work, a lab-on-paper cathode photoelectrochemical (PEC) sensing platform was constructed for ultrasensitive microRNA-141 (miRNA-141) assay using cascaded multiple photo-active structures as signal generators and hemin/Pt nanoparticle (Pt NP) trunk-branching-decorated DNA dendrimers as signal reinforcers. Specifically, pyramid-like Cu