We describe here design, synthesis, and biological evaluation of a series of highly potent HIV-1 protease inhibitors containing stereochemically defined and unprecedented tricyclic furanofuran derivatives as P2 ligands in combination with a variety of sulfonamide derivatives as P2' ligands. These inhibitors were designed to enhance the ligand-backbone binding and van der Waals interactions in the protease active site. A number of inhibitors containing the new P2 ligand, an aminobenzothiazole as the P2' ligand and a difluorophenylmethyl as the P1 ligand, displayed very potent enzyme inhibitory potency and also showed excellent antiviral activity against a panel of highly multidrug-resistant HIV-1 variants. The tricyclic P2 ligand has been synthesized efficiently in an optically active form using enzymatic desymmetrization of meso-1,2-(dihydroxymethyl)cyclohex-4-ene as the key step. We determined high-resolution X-ray structures of inhibitor-bound HIV-1 protease. These structures revealed extensive interactions with the backbone atoms of HIV-1 protease and provided molecular insights into the binding properties of these new inhibitors.The effective prevention of plant bacterial infections has been complicated and challenged by unceasing bacterial resistance. The application of traditional bactericides has achieved certain effects to alleviate this situation. However, these chemicals also have limitations, such as short half-life in reality, limited bioavailability, and pollutant emission from their formulations. These disadvantages drive the demand for promoting antibacterial therapeutics. Self-assembled nanostructures based on amphiphiles have inherently versatile characteristics, including high durability, good bioavailability, sustained release, and regenerability. As such, they have garnered wide interest because of these advantages that may serve as a feasible platform for the management of pathogenic infections. Flexible tuning of the shapes of these nanostructures by manipulating noncovalent driving forces consequently results in different levels of antibacterial activity. Herein, an antibacterial amphiphile, 1-[11-(9-anthracenylmethoxy)-11-oxoundecyl]pyridinium bromide (AP), was assembled into microfilms in screening medium. Hierarchical nanofibers were constructed by introducing an electron-deficient trinitrofluorenone (TNF) molecule into the assembling system directed by charge-transfer (CT) interactions to further investigate the contribution of aggregate shape to bioactivity. Biological evaluation revealed that antibacterial efficacy improved after CT complex formation. This study provides an innovative platform for developing versatile assembled structures for restraining the propagation of plant pathogens and an improved understanding of the actual interplay between the self-assembly and antibacterial ability of bactericides at the supramolecular level.Nine new and nineteen known compounds were isolated and identified from Rosmarinus officinalis under the guidance of bioassay and LCMS. They all belonged to abietane diterpenoids which enriched the types of compounds in R. officinalis, especially the discovery of a series of 20-norabietane diterpenoids (4, 6-9, and 26-27). The antioxidative damage activity of the compounds was tested on H2O2 damaged SH-SY5Y cells. Compounds 5, 6, and 7 presented moderate ability for promoting the growth of damaged cells. Compounds 10, 11, 13-20, 27, and 28 displayed a high antioxidative damage effect whose cell viability rates were more than 80%. https://www.selleckchem.com/products/msab.html The antioxidative damage effect of 11, 16, 18, and 20 were higher than that of EGCG (positive control) in which 11, 18, and 20 were the acetylated derivatives of carnosic acid (10), 7α-methoxy-isocarnosol (16), and carnosol (19), respectively. It suggested that 10-carboxyl/formyl of abietane diterpenoids was essential for maintaining the antioxidative damage activity and the adjacent hydroxyl groups on the benzene ring was less important for holding the bioactivity. These acetylated derivatives with high bioactivity and stability could be regarded as new sources of antioxidants or antioxidative damage agents being used in the food and medical industry.Seven new lactam ent-kaurane diterpenoids, cafemide A-G (1-7), were isolated form roasted beans of Coffea arabica. Their structures were elucidated by extensive spectroscopic analysis including 1D, 2D NMR (HSQC, HMBC, 1H-1H COSY, and ROESY), HRESIMS and IR spectra. They were divided into subtype I-III according to the structure. Further, LC-MS/MS based molecular network was used for the excavation of trace lactam type diterpenoids, seven (8-14) subtype II diterpenoids were successfully identified. In addition, a variety of other subtypes of N-containing diterpenoids have been proven in roasted coffee. Compound 1, 2, 3, 5, 7 showed significant inhibitory effect on α-glucosidase with an IC50 value of 8.28±0.62 μM, 38.23±8.87 μM, 28.94±1.42 μM, 12.44±1.37 μM and 22.2±5.34 μM, respectively. To best of our knowledge, this is the first time that N-containing diterpenoids have been reported in coffee.Among the three key active components (KACs) of Magnolia officinalis bark extract (ME), 4-O-methylhonokiol (MHNK) and honokiol (HNK) showed higher antiproliferation activities than magnolol (MGN) in the oral squamous cancer cell lines (Cal-27, SCC-9 and SCC-4). Oral bioavailabilities of ME-KACs were poor ( less then 0.2%) in C57BL/6 mice primarily due to their extensive first-pass phase II metabolism and poor solubilities. High plasma concentration of glucuronides upon oral administration and faster rate of glucuronidation by intestinal microsomes indicated intestine as one of the major metabolic organs for ME-KACs. Despite the increase in bioavailabilities of ME-KACs (~8-10-folds) and decrease in AUC0-24 of glucuronides (~10-folds) upon ME solubility enhancement, systemic exposure of ME-KACs failed to improve meaningfully. In conclusion, we propose a quality-controlled and chemically-defined ME mixture, containing an optimized ratio of three KACs, delivered locally in the oral cavity as the most promising strategy for ME use as an oral cancer chemopreventive dietary supplement.