Design, synthesis and in vitro evaluation of a series thiazolidinediones analogs as PPAR modulators

A series of thiazolidinediones analogs,as PPAR modulators,were designed,synthesized and evaluated in vitro.     

Microwave-assisted synthesis,antimicrobial, antiquorum-sensing and cytotoxic activities of a new series of isatin-β-thiocarbohydrazones

Abstract

New isatin-β-thiocarbohydrazone hybrids 4-17 were designed relied on isatin scaffold to generate various analogs with expected antimicrobial activity. The new hybrids were estimated for antibacterial effectiveness over S. aureus, B. cereus and E. coli, and antifungal efficacy over C. albicans and A. fumigatus. Compound 14 evinced the highest efficacy over A. fumigatus and C. albicans. In addition, 5 and 12 showed eminent efficacy toward A. fumigatus, where compounds 4, 7, 9, 11, 13, 15 and 16 exhibited moderate activity over the same fungus. Moreover, 6 and 9 displayed moderate activity over C. albicans. The new compounds were also estimated for antiquorum-sensing effectiveness against C. violacium, where compound 17 showed interesting activity. In vitro cytotoxicity assay of the new analogs was done over Hela and COS-7 cancer cell lines. All analogs have IC₅₀ values >50?μM toward both cell lines.     

DMF-dimethyl sulfate as a new reagent for the synthesis of β-lactams

A number of 2-azetidinones were synthesized in good to excellent yields by a novel reaction between Schiff bases, substituted acetic acids and alkoxymethylene-N,N-dimethyliminium salts, the adduct formed from DMF and O-alkylating agents. The advantages of this new method are mild reaction conditions, low cost, avoiding the use of chlorinating agents and easy purification of the products. The best results were obtained when DMF and dimethyl sulfate were used at room temperature.     

β-Cyclodextrin conjugated magnetic nanoparticles as a novel magnetic microvessel and phase transfer catalyst: synthesis and applications in nucleophilic substitution reaction of benzyl halides

This paper presents a feasible protocol for the preparation of β-cyclodextrin conjugated Fe₃O₄ magnetic nanoparticles as an efficient microvessel and host system for nucleophilic substitution reaction of benzyl halides in water. No evidence for the formation of by-product for example isothiocyanate or benzyl alcohol was observed and the products were obtained in pure form without further purification. The characteristics results of FT-IR, XRD, TGA and SEM shows that β-CD is grafted onto Fe₃O₄ nanoparticles. The nanomagnetic catalyst could be readily separated from solution via application of an external magnet, allowing straightforward recovery and reuse.     

Design and evaluation of folate-appended methyl-��-cyclodextrin as a new antitumor agent

Methyl-??-cyclodextrin (M-??-CyD) is widely used as a raft disrupting agent through extraction of cholesterol from lipid rafts which are highly expressed in cell membranes of tumor cells, but it does not have tumor cell-selective action. Meanwhile, the widespread use of folic acid (FA) as a tumor-targeting ligand has been known, because folate receptor (FR) overexpresses in various kinds of epithelial tumor cells. In the present study, in order to obtain more tumor cell-selectivity and antitumor activity of M-??-CyD, we designed folate-appended M-??-CyD (FA-M-??-CyD), and evaluated its physicochemical properties and antitumor activity. The ¹H-NMR study demonstrated that FA-M-??-CyD having average degree of substitution of FA (DSF) of 1.0 was prepared. In addition, FA-M-??-CyD (DSF 1.0) was found to be amorphous in a solid state and surface-active. Importantly, FA-M-??-CyD (DSF 1.0) had potent cytotoxicity, compared to M-??-CyD in KB cells, but not in A549 cells. These results suggest that FA-M-??-CyD (DSF 1.0) has the potential as a novel antitumor agent.     

Interactions of amphiphilic drugs withα-,β-, andγ-cyclodextrins

The association of several amphiphilic drugs with -, -, and -cyclodextrins has been measured by use of drug-sensitive electrodes. Drugs investigated are hydrochlorides of chlorpromazine, dibucaine, tetracaine, and procaine, and valethamate bromide. Each drug forms the drug:cyclodextrin=11 complex with - and -cyclodextrin, and both the 11 and 21 complex with -cyclodextrin, except valethamate which only forms the 11 complex. The strength of the 11 complex formations is in the order of CyD>-CyD>-CyD. The association constant of the 21 complex in drug--CyD is larger than that of 11 complex. The free energy change of the conplex formation has a positive correlation with that of the micelle formation of drugs. The deviation from this relation is explained in terms of fittability of the bulky hydrophobic group of drugs into the cyclodextrin's cavity. The free energy change for the complex formation between chlopromazine or valethamate and -CyD is governed by the enthalpy term and not by the entropy term which controls the surfactant--CyD interactions.     

Design and synthesis of novel α-aminoamides derivatives as Nav1.7 inhibitors for antinociception

Three novel series of α-aminoamides derivatives were designed and synthesized based on ralfinamide,and their Nav1.7 inhibitory activities were evaluated using manual patch clamp electrophysiology. Active compounds inhibited Nav1.7 with half maximal inhibitory concentration(IC50) values ranging from2.9 μmol/L to 21.4 μmol/L. Among them, the most potent compound 19h exhibited about 12-fold potency better than ralfinamide. The investigation of their structure-activity relationship gives a strategy ...     

Design of new super-high birefringent isothiocyanato bistolanes – synthesis and properties

We report the synthesis of new laterally ethyl-substituted high birefringent phenylethynyltolane liquid crystals with alkylsulphanyl chain and isothiocyanate terminal group. The thermal and optical properties such as birefringence are measured and discussed based on their molecular structures. The compounds exhibit birefringence (Δn) in the range of 0.63–0.75 and are expected to be excellent components of high birefringent nematic mixtures for various applications.     

Design, synthesis and in vitro evaluation of phenylbenzamidine derivatives as SSRIs

A series of phenylbenzamidine analogs were synthesized and tested for their biological activities of inhibiting the reuptake of 5- HT. All of them were new compounds, and their structures were confirmed by 1HNMR, MS and XRD.     

Ionic liquids as phase transfer catalysts: Enhancing the biphasic extractive epoxidation reaction for the selective synthesis of β-O-glycosides

Ionic liquids promoted the direct epoxidation of glycals acting as PTC. 1,2-anhydrosugars were prepared by the oxidation of glycals under biphasic conditions with dimethydioxirane generated in situ from oxone/acetone and amphiphilic IL’s as catalysts. β-O-glycosides were synthesized in good yields by the nucleophilic ring opening of epoxy carbohydrate derivatives. Also, 3,4,6-benzyl protected carbohydrates and β-N-glycosides could be prepare by this method.     

Synthesis and biological evaluation of a new series of histone deacetylases inhibitors

Histone deacetylases （HDACs） play an important role in tumorigenesis. Inhibition of HDACs is considered as a potent strategy for cancer therapy. Two lead compounds （ja and jb） were found to have activities against HDACs with IC50 at about 15 μmol/L. Then a new series of hydroximic acid derivatives were designed and synthesized based on them. The HDACs activity assay in vitro found that compounds J04 and ,109 are nearly as potent as the positive control drug Zolinza.     

Pigments with improved properties – microreaction technology as a new approach for synthesis of pigments –

Clariant, as an important pigment producer forces the investigation of new pigments with improved qualities and properties to fulfill the rising tomorrow's demands of customers. For these reasons, new production ways like microreaction technology are included. This paper focuses on results obtained in manufacturing pigments in a lab-scale microreactor as well as in a microreactor pilot plant. Investigations of the diazotation, azo-coupling and laking steps of pigments have shown not only the principle feasibility of these reactions in laboratory microreactors but also significant improvement of coloristic properties. The microreactor pilot plant, realized by the concept of numbering-up instead of conventional scaling-up process, allowed more detailed investigations of the complete azo-pigments synthesis under production conditions.     

Design and efficient synthesis of novel haptens and complete antigens for the AOZ, a toxic metabolite of furazolidone

A good strategy was brought forward for designing efficient haptens and complete antigens for 3-amino-2-oxazolidinone (AOZ). Haptens designed newly were achieved facilely in good yield by using LiCI-N(Et)_3 as new catalysis system,the structure of which was elucidated by spectroscopy analysis,such as NMR and MS.Novel antigens for AOZ were prepared successfully by convenient active ester method.The ratios of haptens 3 and 4 to carrier proteins were proven respectively as 41:1(5a),39:1(6a),11:1(5b) and 9:1(6b) by trinitrobenzene sulfonic acid(TNBS) method.The results of indirect competitive ELISA (ic-ELISA) of antiserums indicated that the haptens with a short unsaturated side chain can evoke specific immune response effectively.     

Design and synthesis of cholesterol-bonded fullerene and porphyrin derivatives for the preparation of a self-assembled donor–acceptor system

The cholesterol-bonded fullerene and porphyrin derivatives were synthesised and characterised. Donor–acceptor thin films were self-assembled through the interaction between cyclodextrin and the cholesterol groups on porphyrin and fullerene derivatives. These uniform films were characterised by ultraviolet–visible and fluorescence spectroscopies. Scanning electron microscopy indicated that the self-assembled film had a chain-like fibre structure with the chains having a diameter of about 50 nm. The intermolecular interaction between chromophores and the formation of complex based on cholesterol and cyclodextrin were proven by the quenching of fluorescence due to the charge transfer from porphyrin moieties to the fullerene units.     

Cyclopentadiene-based Brønsted acid as a new generation of organocatalyst for transfer hydrogenation of 2-substituted quinoline derivatives

A simple and readily available cyclopentadiene-based Brønsted acid was employed to catalyze the transfer hydrogenation of 2-substituted quinolines using Hantzsch ester as the hydrogen source. This conceptually new designed organocatalyst demonstrates remarkably high efficiency for this transformation and a variety of substituted 1,2,3,4-tetrahydroquinoline derivatives were afforded in excellent yields under mild reaction conditions.     

Design,synthesis and structure of new dendritic melamines. First use of a tandem C-2-substituted serinol—O,O-masked 4-piperidone as a peripheral unit in iterative synthesis

The iterative chemoselective amination of cyanuric chloride to dimers of new G-2 dendritic N-substituted-2,4,6-triamino-s-triazines (melamines) having C-2-substituted 2-aminopropane-1,3-diols (‘serinols’) in tandem with the ethylene ketal of 4-piperidone as peripheral units is reported. The structure as a function of increasing molecular size was studied by NMR spectroscopy, DFT calculation and AFM imaging. A concise nomenclature defining the restricted rotational phenomena about the newly created C(s-triazine)–N(exocyclic) partial double bonds, seen as axes of (pro)diastereomerism, is used. We propose a new form of frontier rotamerism for the dendrimer surface, which operates over a long range.     

FT-IR and raman spectra of a series of metallo-β-cyclodextrin complexes

A series of metallo--CD complexes were prepared and formulated as [M₂(OH)₂ -CD·2 H₂O] ^n– . Changes in the FT-IR and Raman Spectra of-CD on coordination may be taken as evidence for complexation and support for a hydroxy bridged binuclear structure. Further support was obtained from uv/visible and magnetic moment measurements.     

Oxalic acid as a simple and efficient organocatalyst for three-component synthesis ofα-amino nitriles

A simple,efficient,and general method has been developed for the synthesis ofα-amino nitriles.Oxalic acid as a BrФnsted acid promotes the addition of TMSCN to various imines(generated in situ).