Extraction and Purification, Structural Characterization and Biological Activity of a Polysaccharide, PRP-1, from Plumeria rubra.

Polysaccharides derived from the flowers of Plumeria rubra (PRP) have shown a variety of beneficial effects on improving human health. However, the structural features and bioactivities of PRP remain unclear. A novel neutral polysaccharide (named PRP-1) with a molecular weight of 23 kDa was extracted and purified from the flowers of P. rubra. PRP-1 was consisted of arabinose, galactose, glucose, xylose and mannose, with a molar ratio of 1.49: 27.89: 50.24: 13.02: 7.36. The structural characterization based on the methylation and 1D/2D nuclear magnetic resonance analyses indicated that PRP-1 was composed of →4)-Glcp-(1→, →4,6)-Glcp-(1→, →4)-Galp-(1→, →2)-Galp-(1→, t-Gal(p), →4)-Manp-(1→, →4,6)-Manp-(1→, t-Man(p), →2)-Xylp-(1→, and t-Xyl(p). Scanning electron microscopy revealed that PRP-1 possess a compact three-dimensional curling network structure in the terms of morphology. PRP-1 exhibited anti-inflammatory activity, which have moderate inhibitory effects on TNF-α and IL-6 production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. In addition, PRP-1 showed ABTS, OH radicals scavenging and the Fe2+ chelating effects in a concentration dependent manner. In α-glucosidase inhibition assay, PRP-1 did not exhibit inhibitory activity. Overall, these results provide a scientific basis for the utilization of the flowers of P. rubra as a potential functional food ingredient.

Molecular Engineering on Solvation Structure of Carbonate Electrolyte toward Durable Sodium Metal Battery at -40 °C.

Carbonate electrolytes have excellent chemical stability and high salt solubility, which are ideally practical choice for achieving high-energy-density sodium (Na) metal battery at room temperature. However, their application at ultra-low temperature (-40 °C) is adversely affected by the instability of solid electrolyte interphase (SEI) formed by electrolyte decomposition and the difficulty of desolvation. Here, we designed a novel low-temperature carbonate electrolyte by molecular engineering on solvation structure. The calculations and experimental results demonstrate that ethylene sulfate (ES) reduces the sodium ion desolvation energy and promotes the forming of more inorganic substances on the Na surface, which promote ion migration and inhibit dendrite growth. At -40 °C, the Na||Na symmetric battery exhibits a stable cycle of 1500 hours, and the Na||Na3 V2 (PO4 )3 (NVP) battery achieves 88.2 % capacity retention after 200 cycles.

Discovery of Aryl Benzoyl Hydrazide Derivatives as Novel Potent Broad-Spectrum Inhibitors of Influenza A Virus RNA-Dependent RNA Polymerase (RdRp).

Influenza A viruses possess a high antigenic shift, and the approved anti-influenza drugs are extremely limited, which makes the development of novel anti-influenza drugs for the clinical treatment and prevention of influenza outbreaks imperative. Herein, we report a series of novel aryl benzoyl hydrazide analogs as potent anti-influenza agents. Particularly, analogs 10b, 10c, 10g, 11p, and 11q exhibited potent inhibitory activity against the avian H5N1 flu strain with EC50 values ranging from 0.009 to 0.034 µM. Moreover, compound 11q exhibited nanomolar antiviral effects against both the H1N1 virus and Flu B virus and possessed good oral bioavailability and inhibitory activity against influenza A virus in a mouse model. Preliminary mechanistic studies suggested that these compounds exert anti-influenza virus effects mainly by interacting with the PB1 subunit of RNA-dependent RNA polymerase (RdRp). These results revealed that 11q has the potential to become a potent clinical candidate to combat seasonal influenza and influenza pandemics.

Design and synthesis of heteroaromatic-based benzenesulfonamide derivatives as potent inhibitors of H5N1 influenza A virus.

Influenza A virus is an enveloped negative single-stranded RNA virus that causes febrile respiratory infection and represents a clinically challenging threat to human health and even lives worldwide. Even more alarming is the emergence of highly pathogenic avian influenza (HPAI) strains such as H5N1, which possess much higher mortality rate (60%) than seasonal influenza strains in human infection. In this study, a novel series of heteroaromatic-based benzenesulfonamide derivatives were identified as M2 proton channel inhibitors. A systematic investigation of the structure-activity relationships and a molecular docking study demonstrated that the sulfonamide moiety and 2,5-dimethyl-substituted thiophene as the core structure played significant roles in the anti-influenza activity. Among the derivatives, compound 11k exhibited excellent antiviral activity against H5N1 virus with an EC50 value of 0.47 µM and selectivity index of 119.9, which are comparable to those of the reference drug amantadine.

Synthesis and structure-activity relationship study of arylsulfonamides as novel potent H5N1 inhibitors.

H5N1 virus, one subtype of highly pathogenic influenza A virus in human infection, has recently received attention due to its unpredictable and high mortality. In this study, a series of arylsulfonamide derivatives were identified as improved H5N1 inhibitors for the influenza treatment by systematic structure-activity relationship investigation. Among them, the most potent H5N1 inhibitor 3h exhibited excellent antiviral activity against H5N1 virus with EC50 value of 0.006 µM and selectivity index 33543.3. Moreover, the molecular docking of 3h with M2 proton channel protein provides practical way for understanding the inhibition of H5N1 with this kind of compounds.