Cyclodextrin-based supramolecular nanogels decorated with mannose for short peptide encapsulation.

Nanogels are aqueous dispersions of hydrogel particles formed by physically or chemically cross-linked polymer networks of nanoscale size. Herein, we devised a straightforward technique to fabricate a novel class of physically cross-linked nanogels via a self-assembly process in water involving α-cyclodextrin and a mannose molecule that was hydrophobically modified using an alkyl chain. The alkyl chain-modified mannose was synthesized in five steps, starting with D-mannose.

Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity.

Our previous study found that desmethylxanthohumol () inhibited α-glucosidase in vitro. Recently, further investigations revealed that dehydrocyclodesmethylxanthohumol () and its dimer analogue rottlerone () exhibited more potent α-glucosidase inhibitory activity than . The aim of this study was to synthesize a series of rottlerone analogues and evaluate their α-glucosidase and DPP-4 dual inhibitory activity.

Synthesis of tetracyclic oxindoles and evaluation of their α-glucosidase inhibitory and glucose consumption-promoting activity.

A series of tetracyclic oxindole derivatives was synthesized by asymmetric 1, 3-dipole reaction in 2-4 steps in 57-86% overall yields. These compounds were evaluated for α-glucosidase inhibitory and glucose consumption-promoting activity in vitro. Compound 4l competitively and reversibly inhibited α-glucosidase (IC = 3.

Molecular basis for transfer RNA recognition by the double-stranded RNA-binding domain of human dihydrouridine synthase 2.

Double stranded RNA-binding domain (dsRBD) is a ubiquitous domain specialized in the recognition of double-stranded RNAs (dsRNAs). Present in many proteins and enzymes involved in various functional roles of RNA metabolism, including RNA splicing, editing, and transport, dsRBD generally binds to RNAs that lack complex structures. However, this belief has recently been challenged by the discovery of a dsRBD serving as a major tRNA binding module for human dihydrouridine synthase 2 (hDus2), a flavoenzyme that catalyzes synthesis of dihydrouridine within the complex elbow structure of tRNA.

Hierarchical supramolecular platelets from hydrophobically-modified polysaccharides and α-cyclodextrin: Effect of hydrophobization and α-cyclodextrin concentration on platelet formation.

Micro- and nano-platelets are a group of particles with typical flat surfaces and hexagonal shape. They are obtained by hierarchical self-assembly in water of α-cyclodextrin and polysaccharides hydrophobically-modified with alkyl chains. It is expected that the formation of well structured and cohesive platelets is driven by the interaction between alkyl chains grafted on polysaccharides and α-cyclodextrin.

Synthesis & α-glucosidase inhibitory & glucose consumption-promoting activities of flavonoid-coumarin hybrids.

Aim: The research of novel and potent antidiabetic agents is urgently needed for the control of the exploding diabetic population. We previously reported the synthesis and antidiabetic activity of natural 8-(6"-umbelliferyl)-apigenin (1), but its antidiabetic targets are not known. Therefore, four series of derivatives were synthesized and evaluated for their antidiabetic activities.

Synthesis of 6-hydroxyaurone analogues and evaluation of their α-glucosidase inhibitory and glucose consumption-promoting activity: Development of highly active 5,6-disubstituted derivatives.

A series of 6-hydroxyaurones and their analogues have been synthesized and evaluated for their in vitro α-glucosidase inhibitory and glucose consumption-promoting activity. These compounds exhibited varying degrees of α-glucosidase inhibitory activity, 11 of them showing higher potency than that of the control standard acarbose (IC=50.30μM).

Netamines O-S, Five New Tricyclic Guanidine Alkaloids from the Madagascar Sponge Biemna laboutei, and Their Antimalarial Activities.

In our continuing program to isolate new compounds from the Madagascar sponge Biemna laboutei, five new tricyclic guanidine alkaloids, netamines O - S (1-5, resp.), have been identified together with the known compounds netamine E (6) and mirabilin J (7). The structures of all new netamines were assigned on the basis of spectroscopic analyses.

Iodine(III)-Mediated Diazidation and Azido-oxyamination of Enamides.

In this study we demonstrate that the combination of bis(tert-butylcarbonyloxy)iodobenzene and lithium azide in acetonitrile allows the diazidation of various enamide substrates. The azido-oxyamination of the same substrates can be carried out in the presence of 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO). Control experiments strongly suggest that this latter process occurs through a shift in nature of the in situ generated electrophilic species from a radical to a cation.

Quorum sensing inhibitors from Leucetta chagosensis Dendy, 1863.

Unlabelled: Sponges are a rich source for investigation of bioactive small molecules. They have been mostly investigated for the search of new pharmacological models or therapeutic agents for the treatment of human diseases. Micro-organisms can also represent a virulent pathogen for marine invertebrates such as sponges, which need to protect themselves against these microbes.

Tandem Catalytic C(sp(3) )-H Amination/Sila-Sonogashira-Hagihara Coupling Reactions with Iodine Reagents.

A new tandem C-N and C-C bond-forming reaction has been achieved through Rh(II) /Pd(0) catalysis. The sequence first involves an iodine(III) oxidant, then the in situ generated iodine(I) by-product is used as a coupling partner. The overall process demonstrates the synthetic value of iodoarenes produced in trivalent iodine reagent mediated oxidations.

Studies on the formal [3 + 2] cycloaddition of aziridines with alkenes for the synthesis of 1-azaspiroalkanes.

The Lewis acid-mediated [3 + 2] cycloaddition of N-sulfonyl- and N-sulfamoylaziridines with alkenes provides a rapid and efficient access to 1-azaspiro[4.n]alkanes. Experimental studies have been combined with DFT calculations to explore the mechanism of the reaction.

Investigation of the complexation of albendazole with cyclodextrins for the design of new antiparasitic formulations.

Albendazole (ABZ) exhibits a potent antiparasitic activity against a broad spectrum of parasites. Unfortunately, the very low water solubility of ABZ (0.2 μg mL(-1), 0.

Robust and low cost uniform (15)N-labeling of proteins expressed in Drosophila S2 cells and Spodoptera frugiperda Sf9 cells for NMR applications.

Nuclear magnetic resonance spectroscopy is a powerful tool to study structural and functional properties of proteins, provided that they can be enriched in stable isotopes such as (15)N, (13)C and (2)H. This is usually easy and inexpensive when the proteins are expressed in Escherichiacoli, but many eukaryotic (human in particular) proteins cannot be produced this way. An alternative is to express them in insect cells.

Transition-metal-free tunable chemoselective N functionalization of indoles with ynamides.

Two unprecedented N functionalizations of indoles with ynamides are described. By varying the electron-withdrawing group on the ynamide nitrogen atom, either Z-indolo-etheneamides or indolo-amidines can be selectively obtained under the same metal-free reaction conditions. The scope and synthetic potential of these reactions, as well as some mechanistic insights provided by DFT calculations, are reported.

Catalytic intermolecular alkene oxyamination with nitrenes.

The Rh(II)-catalyzed intermolecular addition of nitrenes to aromatic and aliphatic alkenes provides vicinal amino alcohols with yields of up to 95 % and complete regioselectivity. This 1,2-oxyamination reaction involves the formation of an aziridine intermediate that undergoes in situ ring opening. The latter is induced by the Rh-bound nitrene that behaves as a Lewis acid.

Diastereoselective three-component vinylogous Mannich reaction of nitrogen heterocycles, acyl/sulfonyl chlorides, and silyloxyfurans/pyrroles.

A one-step, 3-component vinylogous Mannich reaction of trimethylsilyloxyfuran or N-protected tert-butyldimethylsilyloxypyrrole with a variety of nitrogen-containing heterocycles in the presence of diverse electrophiles is described. The reaction products were generally obtained in high yields and as a single diastereoisomer having the (R*,R*) relative configuration based on crystallographic studies of several derivatives. Several azaheterocycles were successfully used for this reaction, such as isoquinolines, quinoline, phenanthridine, quinazoline, phthalazine, and β-carboline, and electrophiles included acetyl chloride, methyl chloroformate, methyl chloromalonate, 2-bromobutanoyl chloride, and arylsulfonyl chlorides.

(3R,4S)-3-Methyl-4-phenyl-2-[(R)-1-phenyl-eth-yl]-3,4-di-hydro-isoquinolin-2-ium tetra-fluorido-borate.

The title salt, C24H24N(+)·BF4 (-), is one of two possible dias-tereoisomers having a different configuration of the asymmetric centre in the α-phenyl-ethyl substituent, whose absolute configuration was established to be R. The two phenyl substituents of the cation have a cofacial orientation, albeit with a long centroid-centroid separation of 4.129 (3) Å.

Reaction of quinones and guanidine derivatives: simple access to bis-2-aminobenzimidazole moiety of benzosceptrin and other benzazole motifs.

A new strategy for the synthesis of 2-aminobenzimidazol-6-ols via a reaction of quinones with guanidine derivatives is reported. Sequential application of this methodology provided a simple access to the first benzosceptrin analogue bearing a bis-2-aminoimidazole moiety. A concomitant addition of two guanidines to the naphtho[1',2':4,5]imidazo[1,2-a]pyrimidine-5,6-dione, which includes the redox neutral debenzylation and guanidine-assisted cleavage of the 2-aminopyrimidine part resulted in the synthesis of the free challenging contiguous bis-2-aminoimidazole moiety of benzosceprins in one step.

Concise synthesis of didebromohamacanthin A and demethylaplysinopsine: addition of ethylenediamine and guanidine derivatives to the pyrrole-amino acid diketopiperazines in oxidative conditions.

Oxidative nucleophilic addition of ethylenediamine and guanidine derivatives to pyrrole-amino acid diketopiperazines was shown to provide substituted 5,6-dihydro-2(1H)-piperazinones, quinoxalinones, and 2-aminoimidazolones. On the basis of this methodology, a concise approach to natural products didebromohamacanthin A and demethylaplysinopsine has been demonstrated.

Virtual screening of the SAMPL4 blinded HIV integrase inhibitors dataset.

Several combinations of docking software and scoring functions were evaluated for their ability to predict the binding of a dataset of potential HIV integrase inhibitors. We found that different docking software were appropriate for each one of the three binding sites considered (LEDGF, Y3 and fragment sites), and the most suitable two docking protocols, involving Glide SP and Gold ChemScore, were selected using a training set of compounds identified from the structural data available. These protocols could successfully predict respectively 20.

Three-component reaction between alkynes, elemental sulfur, and aliphatic amines: a general, straightforward, and atom economical approach to thioamides.

A general, straightforward, and atom-economical three-component synthesis of thioamides from alkynes, elemental sulfur, and aliphatic amines has been developed.

Cobalt- and iron-catalyzed redox condensation of o-substituted nitrobenzenes with alkylamines: a step- and redox-economical synthesis of diazaheterocycles.

A wide variety of functionalized 2-aryl benzimidazoles can be prepared by a solvent-free cobalt- or iron-catalyzed redox condensation of 2-nitroanilines and benzylamines. The cascade including benzylamine oxidation, nitro reduction, condensation, and aromatization occurs without any added reducing or oxidizing agent. The method can be extended to other alkylamines as reducing components or 2-nitrobenzamides as oxidizing components when using an iron/sulfur catalyst to afford various diazaheterocycles.