Dentonholgersen4573

The ability of alkylseleno/alkyltelluroacetylenes such as bis(selenomethylethynyl)-perfluorobenzene (4F-Se) to act as a ditopic chalcogen bond (ChB) donor in co-crystals with ditopic Lewis bases such as 4,4'-bipyridine is extended here to the octafluorobiphenylene analog, 4,4'-bis(selenomethylethynyl)-perfluorobiphenyl (8F-Se), with the more electron-rich 4,4'-bipyridylethane (bpe), showing in the 11 (8F-Se)•(bpe) co-crystal a shorter and more linear C-Se•••N ChB interaction than in (4F-Se)•(bpe), with Se•••N distances down to 2.958(2) Å at 150 K, i.e., a reduction ratio of 0.85 vs. the van der Waals contact distance.Prolonged exposure to cold temperatures often results in a relatively low flowering rate in litchi (Litchi chinensis Sonn.) trees with younger leaves. This study aimed to verify the impact of stem girdling on litchi flowering by identifying and characterizing the induced metabolic changes. After a 60 day exposure to cold treatment at 15 °C/10 °C (12 h/12 h), the flowering rate of the girdled trees was 100%, while that of the non-girdled trees was 20%, indicating that girdling improved litchi flowering at its turning stage. The metabolic profiles of litchi leaves with and without stem girdling during floral induction were compared and 505 metabolites potentially associated with litchi flowering were detected. Most metabolites were involved in the metabolism of starch and sucrose, fatty acid, and phenylpyruvic acid. The metabolic pathways concerned with the biosynthesis of epinephrine, sucrose, and d-maltose were induced in leaves after girdling treatment. 2-Aminoethyl The level of galactitol, phenylpyruvic acid, acetyl-CoA, linoleic acid, alpha-linolenic acid, and 13-HPOT biosynthesis remained stable in the leaves from girdled trees but changed drastically in the leaves from non-girdled trees. In addition, 379 metabolites concerning flowering rate were characterized. Metabolism pathways of starch and sucrose, galactose, and linoleic acid are of great significance to the flowering of litchi. Linoleic acid exhibited the most significant variations between girdled trees and non-girdled trees with fold changes of up to 13.62. These results contribute to understanding the biological mechanism of litchi floral induction and the metabolic changes after stem girdling.Tubulin has been regarded as an attractive and successful molecular target in cancer therapy and drug discovery. Vicinal diaryl is a simple scaffold found in many colchicine site tubulin inhibitors, which is also an important pharmacophoric point of tubulin binding and anti-cancer activity. As the continuation of our research work on colchicine binding site tubulin inhibitors, we designed and synthesized a series of diarylamide N-containing heterocyclic derivatives by the combination of vicinal diaryl core and N-containing heterocyclic skeletons into one hybrid though proper linkers. Among of these compounds, compound 15b containing a 5-methoxyindole group exhibited the most potent inhibitory activity against the tested three human cancer cell lines (MGC-803, PC-3 and EC-109) with IC50 values of 1.56 μM, 3.56 μM and 14.5 μM, respectively. Besides, the SARs of these compounds were preliminarily studied and summarized. The most active compound 15b produced the inhibition of tubulin polymerization in a dose-dependent manner and caused microtubule network disruption in MGC-803 cells. Therefore, compound 15b was identified as a novel tubulin polymerization inhibitor targeting the colchicine binding site. In addition, the results of molecular docking also suggested compound 15b could tightly bind into the colchicine binding site of β-tubulin.The selective inhibition of immunoproteasome is a valuable strategy to treat autoimmune, inflammatory diseases, and hematologic malignancies. Recently, a new series of amide derivatives as non-covalent inhibitors of the β1i subunit with Ki values in the low/submicromolar ranges have been identified. Here, we investigated the binding mechanism of the most potent and selective inhibitor, N-benzyl-2-(2-oxopyridin-1(2H)-yl)propanamide (1), to elucidate the steps from the ligand entrance into the binding pocket to the ligand-induced conformational changes. We carried out a total of 400 ns of MD-binding analyses, followed by 200 ns of plain MD. The trajectories clustering allowed identifying three representative poses evidencing new key interactions with Phe31 and Lys33 together in a flipped orientation of a representative pose. Further, Binding Pose MetaDynamics (BPMD) studies were performed to evaluate the binding stability, comparing 1 with four other inhibitors of the β1i subunit N-benzyl-2-(2-oxopyridin-1(2H)-yl)acetamide (2), N-cyclohexyl-3-(2-oxopyridin-1(2H)-yl)propenamide (3), N-butyl-3-(2-oxopyridin-1(2H)-yl)propanamide (4), and (S)-2-(2-oxopyridin-1(2H)-yl)-N,4-diphenylbutanamide (5). The obtained results in terms of free binding energy were consistent with the experimental values of inhibition, confirming 1 as a lead compound of this series. The adopted methods provided a full dynamic description of the binding events, and the information obtained could be exploited for the rational design of new and more active inhibitors.This work aimed to evaluate the phenolic content and in vitro antioxidant, antimicrobial and enzyme inhibitory activities of the methanol extracts and their fractions of two edible halophytic Limonium species, L. effusum (LE) and L. sinuatum (LS). The total phenolic content resulted about two-fold higher in the ethyl acetate fraction of LE (522.82 ± 5.67 mg GAE/g extract) than in that of LS (274.87 ± 1.87 mg GAE/g extract). LC-MS/MS analysis indicated that tannic acid was the most abundant phenolic acid in both species (71,439.56 ± 3643.3 µg/g extract in LE and 105,453.5 ± 5328.1 µg/g extract in LS), whereas hyperoside was the most abundant flavonoid (14,006.90 ± 686.1 µg/g extract in LE and 1708.51 ± 83.6 µg/g extract in LS). The antioxidant capacity was evaluated by DPPH and TAC assays, and the stronger antioxidant activity in ethyl acetate fractions was highlighted. Both species were more active against Gram-positive bacteria than Gram negatives and showed considerable growth inhibitions against tested fungi.