Expanding indole diversity: direct 1-step synthesis of 1,2-fused indoles and spiroindolines from 2-halo anilines for fast SAR antiviral elucidation against tobacco mosaic virus (TMV)

To systematically investigate the influence of the variation of the original skeletons and spatial configuration of 2,3-fused indole natural products on antiviral activities, two types of structurally novel and potent pseudo-indole natural product derivatives, 1,2-fused indole and spiroindoline, with different substituents were direct synthesized from 2-halo anilines, and their antiviral activities against tobacco mosaic virus (TMV) were evaluated. The results showed that these compounds exhibited good anti-TMV activity, especially 3f, 3g, 3i, 5e, 5h, and 5l, which were more potent than the commercial anti-virus agent ribavirin. An SAR investigation demonstrates that the original ring size, arrangement, and planarity are not optimal; their anti-TMV activities can be improved by skeleton modification and spatial configuration variation. Both of the structurally novel skeletons provide a new template for antiviral studies, which may also provide some useful information for antiviral mechanism elucidation.     

Design,synthesis and activity evaluation of mannose-based DC-SIGN antagonists

In this article, we describe the design, synthesis and activity evaluation of glycomimetic DC-SIGN antagonists, that use a mannose residue to anchor to the protein carbohydrate recognition domain (CRD). The molecules were designed from the structure of the known pseudo-mannobioside antagonist 1, by including additional hydrophobic groups, which were expected to engage lipophilic areas of DC-SIGN CRD. The results demonstrate that the synthesized compounds potently inhibit DC-SIGN-mediated adhesion to mannan coated plates. Additionally, in silico docking studies were performed to rationalize the results and to suggest further optimization.     

Design,synthesis, insecticidal activity,and structure-activity relationship (SAR): studies of novel triazone derivatives containing a urea bridge group based on transient receptor potential (TRP) channels

Numerous compounds containing urea bridge and biurea moieties are used in a variety of fields, especially as drugs and pesticides. To search for novel, environmentally benign and ecologically safe pesticides with unique modes of action, four series of novel triazone analogues containing urea, thiourea, biurea, and thiobiurea bridge, respectively, were designed and synthesized, according to various calcium ion channel inhibitors which act on transient receptor potential protein. Their structures were characterized by \({}^{1}\mathrm{H}\) NMR, \({}^{13}\mathrm{C}\) NMR, and HRMS. The insecticidal activities of the new compounds were obtained. The bioassay results indicated that compounds containing a thiourea bridge and a thiobiurea bridge exhibited excellent insecticidal activities against bean aphid. Specifically, compounds \({\mathbf{VIb}}_{15}\), \({\mathbf{VIIb}}_{8}\), and \({\mathbf{VIIb}}_{9}\) exhibited 85, 90, and 95 % activities, respectively, at 10 mg/kg. Compounds \({\mathbf{VIb}}_{14}\) (30 %), \({\mathbf{VIIb}}_{10}\) (35 %), \({\mathbf{VIIb}}_{11}\) (30 %), and \({\mathbf{VIIb}}_{12}\) (40 %) exhibited the approximate aphicidal activity of pymetrozine (30 %) at 5 mg/kg. In addition, some target compounds exhibited insecticidal activities against lepidopteran pests. From a molecular design standpoint, the information obtained in this study could help in the further design of new derivatives with improved insecticidal activities.     

Glycosaminoglycans and glycoconjugates in the adult anuran integument (Lithobates catesbeianus)

Glycosaminoglycans (GAGs) from the integument of Lithobates catesbeianus were biochemically characterized and histochemically localized. Moreover, carbohydrate distribution was investigated using conventional and lectin histochemistry at light microscopy. Hyaluronan (HA), dermatan sulfate (DS) and a heparanoid were found in the integument. Sulfated and carboxylated GAGs were visualized in the Eberth-Katschenko (EK) layer, in the mucous glands, in the hypodermis as well as in the mast cells. Furthermore, glucose and galactose were identified in the integument through thin layer chromatography (TLC) assays. N-Acetyl-β-glucosamine residues were identified in the mucous glandular cells, between the corneum and spinosum strata, in the subepidermal region, and in the EK layer. N-Acetyl-galactosamine residues were evident in the EK layer, corresponding to a residue of the dermatan sulfate chain, which may be related to the collagenous fiber arrangement. These glycoconjugates occurred as secretory glandular products and as dermal structural elements. Moreover, HA and DS are the predominant GAGs in the L. catesbeianus integument. Considering the importance of glycoconjugates, they play a significant role to the integrity of the skin, providing mechanical support for integument cells. In addition, they are important to the water regulation mechanisms, since L. catesbeianus is preferably aquatic.     

Design,synthesis and antifungal activity of (E)-3-acyl-5-(methoxyimino)-1,5-dihydrobenzo[e][1,2]oxazepin-4(3H)-one analogues

Molecular Diversity - Nitrogen- or oxygen-containing organic compounds which have significant antifungal activity, twenty one novel nitrogen or oxygen-containing...     

Design,synthesis and sensor activity of a highly photostable blue emitting 1,8-naphthalimide

This work reports on the design, synthesis and photophysical properties of a highly photostable blue emitting 1,8-naphthalimide, containing hindered amine radical scavenger moiety and a tertiary amine cation receptor. The novel compound was configured as “fluorophore-spacer-receptor” system based on photoinduced electron transfer. Photophysical characteristics of the examined compound were investigated in DMF and water/DMF (4:1, v/v) solution. The ability of the new compound to detect cations was evaluated by the changes in its fluorescence intensity in the presence of metal ions (Cu²⁺, Pb²⁺, Cd²⁺, Ni²⁺, Co²⁺, Fe³⁺ and Zn²⁺) and protons. The presence of metal ions and protons was found to disallow a photoinduced electron transfer resulting in enhancement of the 1,8-naphthalimide fluorescence intensity. Among the tested metal ions only Cu²⁺ was efficiently detected. Also, it is clearly shown that the 2,2,6,6-tetramethylpiperidine fragment, incorporated in the structure of the novel 1,8-naphthalimide, considerably improves the sensor's photostability, sensitivity and selectivity.     

Design and synthesis of novel protein kinase R (PKR) inhibitors

Protein kinase RNA-activated (PKR) plays an important role in a broad range of intracellular regulatory mechanisms and in the pathophysiology of many human diseases, including microbial and viral infections, cancer, diabetes and neurodegenerative disorders. Recently, several potent PKR inhibitors have been synthesized. However, the enzyme’s multifunctional character and a multitude of PKR downstream targets have prevented the successful transformation of such inhibitors into effective drugs. Thus, the need for additional PKR inhibitors remains. With the help of computer-aided drug-discovery tools, we designed and synthesized potential PKR inhibitors. Indeed, two compounds were found to inhibit recombinant PKR in pharmacologically relevant concentrations. One compound, 6-amino-3-methyl-2-oxo-N-phenyl-2,3-dihydro-1H-benzo[d]imidazole-1-carboxamide, also showed anti-apoptotic properties. The novel molecules diversify the existing pool of PKR inhibitors and provide a basis for the future development of compounds based on PKR signal transduction mechanism.     

Parallel synthesis of natural product-like polyhydroxylated pyrrolidine and piperidine alkaloids

The preparation of natural product-like polyhydroxylated pyrrolidine and piperidine alkaloids using a combination of solid– and solution-phase organic synthesis is described. The key intermediates, enantiopure five- or six-membered tri-O-benzyl cyclic nitrones, were efficiently prepared on solid support from accessible chiral furanosides and pyranosides, respectively. The substituent diversity was achieved by a diastereoselective addition of a variety of Grignard reagents to the cyclic nitrones in solution-phase synthesis. All reaction steps and work-up procedures were modified to allow the use of automated equipment. A 36-membered demonstration library with three diversity elements (core, configuration, and substituent) was prepared in good yield and purity.     

A new nano-structured Ni(II) Schiff base complex: synthesis,characterization, optical band gaps,and biological activity

New Ni(II) Schiff base complexes [{Ni(L)(H₂O)Cl} where HL = 2-((pyridin-3-ylmethylene)amino)phenol] have been synthesized using the reflux and sonochemical methods. The nickel oxide NiO nanopowder was obtained from the metal complexes after calcination at 650 °C for 2 h. The Schiff base complexes and NiO powders were characterized in detail. The HL and its metal complexes were depicted high activity towards microorganism and breast carcinoma cells. The inhibitory activity against breast carcinoma (MCF-7) were detected with IC₅₀ = 5.5, 12.5 and 9.6 for HL, complex (1) and complex (2), respectively. The optical band gap energy was 3.6, 3.0 and 2.37 eV for Ni complexes (1), (2) and NiO, respectively. The microstructure of the formed NiO powders appeared as cubic-like structure. Furthermore, magnetic properties of NiO sample were identified and paramagnetic property was found at a room temperature. The saturation magnetization and coercive force for the NiO sample were 0.47 emu/g and 42.68 Oe, respectively.     

Design,synthesis, in silico and biological evaluation of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)hydrazine carboxamides

A series of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)hydrazinecarboxamide derivatives has been successfully designed and synthesized to evaluate their potential as carbonic anhydrase (CA) inhibitors. The inhibitory potential of synthesized compounds against human CAI and CAII was evaluated. Compounds 3a–n exhibited \(\hbox {IC}_{50}\) values between \(1.89{-}415.1\,\upmu \hbox {M}\) against CAI and \(0.62{-}66.9\,\upmu \hbox {M}\) against CAII. Compound 3g was the most active inhibitor, with an \(\hbox {IC}_{50}\) value of \(0.62\,\upmu \hbox {M}\) against CAII. Molecular docking studies of compound 3g with CAII showed this compound fits nicely in the active site of CAII and it interacts with the zinc ion (\(\hbox {Zn}^{2+}\)) along with three histidine residues in the active site. Molecular dynamics simulation studies of compound 3g complexed with CAII also showed essential interactions which were maintained up to 40 ns of simulation. In vivo sub-acute toxicity study using 3g (300 mg/kg) was found non-toxic in adult Wistar rats.     

Graphene-CdS composite, synthesis and enhanced photocatalytic activity

Graphene-CdS (G-CdS) composites were synthesized through a simple solvothermal method. The formed CdS nanospheres were homogeneously scattered on the surface of graphene sheets. Fluorescence quenching effect of the G-CdS composites indicated effective transfer of photo-excited electrons from CdS to graphene, suppressed the recombination of photo-generated electron-hole pairs, so that the enhanced visible light induced photodegradation activity for Rhodamine B (RhB) was achieved. Based on the high photocatalytic activity and well stability, the G-CdS composite containing 70% CdS can be expected to be a practical visible light photocatalyst.     

Design and synthesis of highly stable poly(tetrafluoroethylene)-zirconium phosphate (PTFE-ZrP) ion-exchange membrane for vanadium redox flow battery (VRFB)

Vanadium redox flow battery (VRFB) is a promising technology for large-scale renewable energy storage. Design of ion-exchange membrane (IEM) with desired properties like low-cost, mechanically chemically stable, low vanadium ion permeability and high proton conductivity is one of the major challenges. Here, we report the design and synthesis of novel poly(tetrafluoroethylene)-zirconium phosphate (PTFE-ZrP) asymmetric IEM using a simple brush coating method. XRD results confirmed the presence of α-ZrP crystalline phase onto the top layer of the membrane. Excellent mechanical strength was observed with burst pressure of 3.22 × 10⁵ N m^?2. Oxidative stability of membrane in Fenton’s reagent was much better than Nafion-115. Vanadium ion (V⁴⁺) permeability of the membrane was more than three times lower than that of Nafion-115. Single-cell VRFB with PTFE-ZrP membrane showed ～80% energy efficiency below 30 mA cm^?2. Very high columbic efficiency ～100% of VRFB with PTFE-ZrP membrane confirmed little contamination of electrolyte due to cross-mixing.     

Design,synthesis and SAR of antitubercular benzylpiperazine ureas

Molecular Diversity - N-furfuryl piperazine ureas disclosed by scientists at GSK Tres Cantos were chosen as antimycobacterial hits from a phenotypic whole-cell screen. Bioisosteric replacement of...     

Characterization of keyhole limpet hemocyanin (KLH) glycans sharing a carbohydrate epitope with Schistosoma mansoni glycoconjugates

Keyhole limpet hemocyanin (KLH) is known to share carbohydrate epitopes with Schistosoma mansoni. In order to define the structural basis for the observed serological cross-reactivity, KLH glycans were released either by enzyme treatment or by hydrazinolysis and probed with a rabbit hyperimmune serum directed against S. mansoni egg antigen. Both major, non-reacting oligosaccharide species as well as the minor compounds recognized were isolated by two-dimensional high performance liquid chromatography and in part by lectin affinity chromatography, and characterized by mass spectrometry. The results revealed that KLH carries predominantly high mannose-type glycans as well as short sugar chains. As a characteristic feature, a number of the latter glycans contained a Gal(beta1-6)Man-unit, which has not yet been found in glycoprotein-N-glycans. Oligosaccharides cross-reacting with schistosomal glycans comprised a terminal Fuc(alpha1-3)GalNAc-motif, which appears to represent the main carbohydrate epitope mediating cross-reactivity of KLH with glycoconjugates from S. mansoni.     

A practical and efficient synthesis of bis(indolyl)methanes in water,and synthesis of di-, tri-, and tetra(bis-indolyl)methanes under thermal conditions catalyzed by oxalic acid dihydrate

A simple, clean, and highly efficient green protocol has been developed for synthesis of bis(indolyl), di(bis-indolyl), and tris-indolyl methanes by the reaction of indole with aldehydes and ketones irn the presence of oxalic acid dihydrate [(CO₂H)₂·2H₂O] and N-cetyl-N, N, N-trimethylammonium bromide (CTAB) in water. Also, tri(bis-indolyl) and tetra(bis-indolyl)methanes as new bis(indolyl)methanes were prepared under thermal conditions.     

Design, synthesis and characterisation of interfaces in engineering materials

Examples of recent work where novel interfaces have been designed and synthesised in a variety of materials are presented. The significance of characterisation using transmission electron microscopy and atom probe field ion microscopy is emphasised as a key tool for providing feedback into the design and synthesis. This is particularly true for complex multicomponent materials such as discussed here, where the materials design is largely concerned with achieving the right blance of solute across specific interfaces. The discussion focuses on precipitate/matrix inter-faces in turbine rotor steels used for power generation and internal interfaces in precipitation in an experimental multi-component aluminium alloy.     

Exploring the potential of applying infrared vibrational (micro)spectroscopy in ergot alkaloids determination: Techniques,current status,and challenges

Ergot alkaloids (EA) are toxins produced mainly by Claviceps fungi and are considered as one of the most important groups of mycotoxins. Rapid and reliable detection techniques are urgently required by producers, importers and market regulators. As a promising alternative to conventional wet chemistry, infrared (IR)-based techniques are non-destructive, rapid and cost-effective. However, very limited studies on the qualitative or quantitative analysis of ergot or EA in food or feed based on IR vibrational spectroscopy have been reported so far. Being a secondary technique, the accuracy of IR method heavily depends on the robustness of chemometrics models. This paper aims to offer a brief overview of the EA issue in food and feed, conventional detection methods, theoretical principles of IR-based techniques and commonly used chemometrics for spectral data processing. In addition, the current application status of IR spectroscopy in ergot research is also considered.