Development of Receptor for Advanced Glycation End Products (RAGE) ligands through target directed dynamic combinatorial chemistry: a novel class of possible antagonists.

RAGE is a transmembrane receptor of immunoglobulin family that can bind various endogenous and exogenous ligands, initiating the inflammatory downstream signaling pathways, including inflammaging. Therefore, RAGE represents an attractive drug target for age-related diseases. For the development of small-molecule RAGE antagonists, we employed protein-templated dynamic combinatorial chemistry (ptDCC) using RAGE's VC1 domain as a template, the first application of this approach in the context of RAGE.

A Novel Natural Siderophore Antibiotic Conjugate Reveals a Chemical Approach to Macromolecule Coupling.

Inspired by natural sideromycins, the conjugation of antibiotics to siderophores is an attractive strategy to facilitate "Trojan horse" delivery of antibiotics into bacteria. Genome analysis of a soil bacterium, found a "hybrid" biosynthetic gene cluster responsible for the production of both an antibiotic, pyridomycin, and a novel chlorocatechol-containing siderophore named chlorodactyloferrin. While both of these natural products were synthesized independently, analysis of the culture supernatant also identified a conjugate of both molecules.

Natural Compounds with Antifungal Properties against and Identification of Hinokitiol as a Promising Antifungal Drug.

is an opportunistic yeast that causes most fungal infections. has become increasingly resistant to antifungal drugs over the past decade. Our study focused on the identification of pure natural compounds for the development of antifungal medicines.

Anti- Drug Candidates Based on Virulence Factors of Malassezia-Associated Diseases.

is a lipophilic unicellular fungus that is able, under specific conditions, to cause severe cutaneous and systemic diseases in predisposed subjects. This review is divided into two complementary parts. The first one discusses how virulence factors contribute to pathogenesis that triggers skin diseases.

Glycated bovine serum albumin for use in feeding trials with animal models - In vitro methodology and characterization of a glycated substrate for modifying feed pellets.

This study investigated different methods to produce N-carboxymethyl-lysine (CML)-enriched bovine serum albumin (BSA) as alternatives to the classical approach using glyoxylic acid (GA) and sodium cyanoborohydride (NaBHCN) which results in toxic hydrogen cyanide (HCN). The reaction of GA (6 mmol/L) and NaBHCN (21 mmol/L) to produce CML remained the most effective with CML yields of 24-35%, followed by 13-24% using 300 mmol/L glyoxal (GO). GA promoted specific modification of lysine to CML, and fewer structural modifications of the BSA molecule compared with GO, as evidenced by fluorescence and proteomic analyses.

Antifungal Properties of Hydrazine-Based Compounds against .

, an opportunistic yeast, is the most common cause of fungal infection. In the past decade, there has been an increase in resistance to existing antifungal drugs, which has necessitated the development of new antifungal agents. In the present study, screening 60 compounds from the JUNIA chemical library enabled us to explore an additional 11 hybrid compounds that contain pyrrolidinone rings and hydrazine moieties for their potential antifungal activities.

Two New Compounds Containing Pyridinone or Triazine Heterocycles Have Antifungal Properties against .

Candidiasis, caused by the opportunistic yeast , is the most common fungal infection today. Resistance of to current antifungal drugs has emerged over the past decade leading to the need for novel antifungal agents. Our aim was to select new antifungal compounds by library-screening methods and to assess their antifungal effects against .

Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug .

Invasive fungal infections represent an expanding threat to public health. During the past decade, a paradigm shift of candidiasis from to non-albicans species has fundamentally increased with the advent of . was identified in 2009 and is now recognized as an emerging species of concern and underscores the urgent need for novel drug development strategies.

Sesamol-based terpenoids as promising bio-sourced crop protection compounds against the wheat pathogen Zymoseptoria tritici.

Background: Research into environmentally friendly alternatives to conventional plant protection products, to promote sustainable agriculture and healthy food, is strongly encouraged.

Results: In this context, 20 naturally occurring terpenoids and phenolic compounds were selected and evaluated in vitro as crop protection compounds against Zymoseptoria tritici, the causal agent of Septoria tritici blotch of wheat. After selection of the most active compounds, some hemisynthetic modifications were conducted to modify their lipophilicity.

Design, synthesis and evaluation of hydrazine and acyl hydrazone derivatives of 5-pyrrolidin-2-one as antifungal agents.

Twenty-eight 5-pyrrolidine-2-ones decorated by hydrazine or acyl hydrazones groups have been designed, synthesized and evaluated as antifungal agents on a panel of twelve fungal strains and three non albicans candida yeasts species which have demonstrated reduced susceptibility to commonly used antifungal drugs. Half of the target compounds exhibited good to high antifungal activities on at least one strain with MIC lower than the control antifungal agent - hymexazol or ketoconazole. 5-Arylhydrazino-pyrrolidin-2-ones were found active and the -NH-NH- linker proved to be essential to maintain the antifungal potential.

Analytical and preparative enantioseparations in supercritical fluid chromatography using different brands of immobilized cellulose tris (3,5-dichlorophenylcarbamate) columns: Some differences.

The aim of this study was to determine the impact of the origin and the manufacturing processes of the chiral stationary phases (CSPs) on their chromatographic behaviors. Hence, four chiral stationary phases based on immobilized tris (3,5-dichlorophenylcarbamate) derivative of cellulose supplied by four different manufacturers were evaluated. A set of twenty-nine compounds, including commercially available and in-house synthesized compounds, with a broad range of lipophilicity and polarity was chosen.

Design, synthesis and antifungal activity of pterolactam-inspired amide Mannich bases.

Pterolactam (5-methoxypyrrolidin-2-one) is a heterocycle naturally occurring in plants. In an attempt to identify antifungal agents, a series of novel Mannich bases of amide derivated from Pterolactam have been designed, synthesized and their antifungal activities were evaluated on a panel of nine fungal strains and three non albicans candida yeasts species which have demonstrated reduced susceptibility to commonly used antifungal drugs. A third of the target compounds exhibited good to high antifungal activities on at least one strain with EC lower than the control antifungal agent.

Amphiphilic azobenzenes: Antibacterial activities and biophysical investigation of their interaction with bacterial membrane lipids.

With the emergence of multi-drug resistant bacteria and hospital-acquired infections, there is an urgent need to develop new antibiotics. Here, we report the synthesis, physico-chemical characterizations, and antimicrobial activity assays of four Azo compounds that differ in their alkyl chain length. The molecular mechanism of their antibacterial activity was investigated by complementary in vitro and in silico biophysical studies.

Performance comparison of chlorinated chiral stationary phases in supercritical fluid chromatography for separation of selected pyrrolidone derivatives.

The effects of two chlorinated chiral stationary phases, namely, Lux Cellulose-2 and Lux i-Cellulose-5, flow-rate, percentage of co-solvent and chemical structures of the compounds on retention and resolution were studied within this article. In this work a backpressure of 150 bar, a temperature of 40 °C and 10% of methanol as co-solvent were chosen as operating conditions. The optimum flow-rate was 2 mL/min.

Separations of antifungal compounds in capillary electrophoresis with two anionic cyclodextrins.

CD-CZE methods were developed for complete stereoisomeric separations of a series of six γ-lactam analogues, of which some were neutral, or cationic depending on the background electrolyte nature. The tested cyclodextrin was the versatile sulfobutylether- β-CD, used either in a phosphate buffer using capillaries dynamically coated with polyethylene oxide or in a borate buffer using uncoated capillaries. Long-end and short-end modes and concentration variations of chiral selectors allowed finding conditions of complete separation of four out of the six derivatives (i.

A Small Aromatic Compound Has Antifungal Properties and Potential Anti-Inflammatory Effects against Intestinal Inflammation.

Resistance of the opportunistic pathogen to antifungal drugs has increased significantly in recent years. After screening 55 potential antifungal compounds from a chemical library, 2,3-dihydroxy-4-methoxybenzaldehyde (DHMB) was identified as having potential antifungal activity. The properties of DHMB were then assessed in vitro and in vivo against overgrowth and intestinal inflammation.

Selective Pinacol-Coupling Reaction using a Continuous Flow System.

The first continuous flow pinacol coupling reaction of carbonyl compounds was successfully achieved within only 2 min during a single pass through a cartridge filled with zinc(0). The optimized method allowed the efficient production of gram-scale value-added compounds with high productivity. The developed methodology is efficient for aromatic or α,β-unsaturated aldehydes but gives moderate results for more stable acetophenone derivatives.

2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs) as human immunodeficiency virus type 1 integrase inhibitors: Influence of the alkylcarboxamide substitution of position 4.

Herein, we report further insight into the biological activities displayed by the 2-hydroxyisoquinoline-1,3(2H,4H)-dione (HID) scaffold. Previous studies have evidenced the marked fruitful effect of substitution of this two-metal binding pharmacophore at position 4 by phenyl and benzyl carboxamido chains. Strong human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors in the low nanomolar range with micromolar (even down to low nanomolar) anti-HIV activities were obtained.

Selective Pinacol Coupling on Regeneratable Supported Acids in Sole Water.

Efficient pinacol coupling was developed in sole water, using a reusable heterogeneous supported acid source and zinc as cheap available metal source. This medium can be easily regenerated up to 10-fold without loss of activity. Moreover, supported acids enhance the selectivity of the pinacol coupling reaction compared with homogeneous acids.

First pinacol coupling in emulsified water: key role of surfactant and impact of alternative activation technologies.

For the first time, the influence of surfactants on the radical pinacol coupling reaction is investigated. The rate and selectivity of this reductive C-C coupling are compared under three different activation technologies: thermal activation, microwave irradiation, and sonication. The use of IgepalCO520, a neutral surfactant, led to the successful conversion of aromatic or α,β-unsaturated aliphatic carbonyl compounds in moderate to excellent yield (55-90 %).

4-Substituted 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as a Novel Class of HIV-1 Integrase Inhibitors.

A series of 2-hydroxy-1,3-dioxoisoquinoline-4-carboxamides featuring an N-hydroxyimide chelating functionality was evaluated for their inhibitory properties against human immunodeficiency virus type 1 integrase (HIV-1 IN). Several derivatives displayed low nanomolar IC50 values comparable to that of the clinically used raltegravir. A marked effect of one compound on both primary IN-catalyzed reactions, strand transfer (ST), and 3' processing (3'-P), emphasizes a novel IN inhibition mechanism establishing it as a potential new generation IN inhibitor.

Micellar catalysis using a photochromic surfactant: application to the Pd-catalyzed Tsuji-Trost reaction in water.

The first example of a Pd-catalyzed Tsuji-Trost reaction, applied in a photochromic micellar media under conventional heating and microwave irradiation, is reported. The surfactant activity and recycling ability were investigated and compared with those of a few commercially available surfactants. The synthetic photochromic surfactant proved to be efficient, recyclable, and versatile for Pd-catalyzed coupling reactions.