Synthesis and Properties of Photoswitchable Carbohydrate Fluorosurfactants

2015 ◽  
Vol 68 (12) ◽  
pp. 1880 ◽  
Author(s):  
Yingxue Hu ◽  
Joshua B. Marlow ◽  
Rajesh Ramanathan ◽  
Wenyue Zou ◽  
Hui Geok Tiew ◽  
...  
Keyword(s):  
Water Solubility ◽  
Cycloaddition Reaction ◽  
Parallel Synthesis ◽  
Head Group ◽  
Responsive Materials ◽  
Good Thermal Stability ◽  
New Class ◽  
Antibacterial Performance ◽  
Broad Interest ◽  
Cis Isomer

We describe the parallel synthesis, photocontrollable surface tension, and antibacterial performance of a new class of carbohydrate fluorosurfactant. Novel fluorosurfactants comprised a mono- or disaccharide head group linked to an azobenzene unit that was variably substituted with a trifluoromethyl group. Fluorosurfactants were rapidly assembled using the venerable CuI-catalysed azide–alkyne cycloaddition reaction and exhibited light-addressable surface activity, excellent water solubility, and selective antibacterial activity against Gram-positive Staphylococcus aureus. Notably, the physicochemical and biological activity of these novel materials was heavily dependent on the nature of the head group and the position of the trifluoromethyl substituent on the azobenzene ring. The UV-adapted cis-isomer of fluorosurfactants displayed good thermal stability at ambient temperature, with little reversion to the stable trans isomer after 16 h. These novel, light-responsive materials should find broad interest in a range of biomedical and technological fields, including drug and gene delivery, self-cleaning oleophobic surfaces, and antibacterial coatings for medical devices.

scholarly journals Structure-Activity Relationship of a New Class of Anti-Hepatitis B Virus Agents

2002 ◽  
Vol 46 (12) ◽  
pp. 4004-4008 ◽  
Author(s):  
Anand Mehta ◽  
Bertha Conyers ◽  
D. L. J. Tyrrell ◽  
Kathie-Anne Walters ◽  
Graham A. Tipples ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Head Group ◽  
New Class ◽  
Chemical Structures ◽  
B Virus ◽  
Ymdd Motif ◽  
Sugar Derivatives ◽  
Relationship Of

ABSTRACT N-Nonyl-deoxy-galactonojirimycin (N-nonyl-DGJ) has been shown to reduce the amount of hepatitis B virus (HBV) produced by tissue cultures under conditions where cell viability is not affected. We show here that the compound N-nonyl-DGJ was effective against lamivudine-resistant HBV mutants bearing the YMDD motif in the polymerase gene, consistent with the compound's activity being distinct from those of nucleoside inhibitors. To better understand the chemical structures that influence its antiviral activity, a series of imino sugar derivatives were made and tested for their antiviral activity against HBV. This work suggests that the antiviral activity of the alkovirs requires an alkyl chain length of at least eight carbons but that the galactose-based head group can be modified with little or no loss in activity.

scholarly journals N-Alkyl Urea Hydroxamic Acids as a New Class of Peptide Deformylase Inhibitors with Antibacterial Activity

2002 ◽  
Vol 46 (9) ◽  
pp. 2752-2764 ◽  
Author(s):  
Corinne J. Hackbarth ◽  
Dawn Z. Chen ◽  
Jason G. Lewis ◽  
Kirk Clark ◽  
James B. Mangold ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antimicrobial Agents ◽  
Enzyme Inhibitor ◽  
Structural Information ◽  
Hydroxamic Acids ◽  
Parallel Synthesis ◽  
Peptide Deformylase ◽  
New Class ◽  
Relationship Analysis ◽  
Starting Point

ABSTRACT Peptide deformylase (PDF) is a prokaryotic metalloenzyme that is essential for bacterial growth and is a new target for the development of antibacterial agents. All previously reported PDF inhibitors with sufficient antibacterial activity share the structural feature of a 2-substituted alkanoyl at the P1′ site. Using a combination of iterative parallel synthesis and traditional medicinal chemistry, we have identified a new class of PDF inhibitors with N-alkyl urea at the P1′ site. Compounds with MICs of ≤4 μg/ml against gram-positive and gram-negative pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae, have been identified. The concentrations needed to inhibit 50% of enzyme activity (IC50s) for Escherichia coli Ni-PDF were ≤0.1 μM, demonstrating the specificity of the inhibitors. In addition, these compounds were very selective for PDF, with IC50s of consistently >200 μM for matrilysin and other mammalian metalloproteases. Structure-activity relationship analysis identified preferred substitutions resulting in improved potency and decreased cytotoxity. One of the compounds (VRC4307) was cocrystallized with PDF, and the enzyme-inhibitor structure was determined at a resolution of 1.7 Å. This structural information indicated that the urea compounds adopt a binding position similar to that previously determined for succinate hydroxamates. Two compounds, VRC4232 and VRC4307, displayed in vivo efficacy in a mouse protection assay, with 50% protective doses of 30.8 and 17.9 mg/kg of body weight, respectively. These N-alkyl urea hydroxamic acids provide a starting point for identifying new PDF inhibitors that can serve as antimicrobial agents.

scholarly journals A NEW CLASS OF IONIC SOLVENTS, ELECTROLYTES AND ENGINEERING FLUIDS BASED ON 1,3-ALKYLMETHYL-1,2,3-BENZOTRIAZOLIUM SALTS

2010 ◽  
Vol 6 (2) ◽  
pp. 111-116 ◽  
Author(s):  
Ahmad Mudzakir
Keyword(s):  
Ionic Liquids ◽  
Single Crystal ◽  
Thermal Analyses ◽  
Spectroscopic Studies ◽  
Electrochemical Analysis ◽  
Electrochemical Characteristics ◽  
Melting Points ◽  
X Ray ◽  
Good Thermal Stability ◽  
New Class

A new series of ionic liquids based on 1,3-alkylmethyl-1,2,3-benzotriazolium cation has been prepared. The spectroscopic, physical and electrochemical characteristics of this family of salts have been investigated with respect to potential usage as ionic solvents, electrolytes and engineering fluids. Incorporation of diverse anions including weak coordinating anion and pseudohalide with this benzotriazolium cation produces ionic liquids with advantageously low melting points and good thermal stability. Thermal analyses of these very stable salts included the determination of melting points (-65 to 164 oC) and decomposition temperatures (up to 291 oC). The electrochemical windows of representative benzotriazolium species has been investigated by cyclic voltammetry and determined to be ~ 3 V. The X-ray single crystal and spectroscopic studies revealed that weak hydrogen-bonding interactions between the benzotriazolium ring protons and the anions are present both in the solid state as well as in solution.   Keywords: ionic liquids, X-ray single crystal, thermal analysis, electrochemical analysis, benzotriazolium salt

scholarly journals Plant-Derived Purification, Chemical Synthesis, and In Vitro/In Vivo Evaluation of a Resveratrol Dimer, Viniferin, as an HCV Replication Inhibitor

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 890 ◽  
Author(s):  
Sungjin Lee ◽  
Karabasappa Mailar ◽  
Mi Il Kim ◽  
Minkyung Park ◽  
Jiseon Kim ◽  
...  
Keyword(s):  
Water Solubility ◽  
Synthesis Method ◽  
Drug Candidate ◽  
In Vivo Evaluation ◽  
New Class ◽  
Pharmacokinetic Properties ◽  
Viral Helicase ◽  
Further Development

Oligostilbenoid compounds, a group of resveratrol multimers, display several anti-microbial activities through the neutralization of cytotoxic oxidants, and by inhibiting essential host and viral enzymes. In our previous study, we identified a series of oligostilbenoid compounds as potent hepatitis C virus (HCV) replication inhibitors. In particular, vitisin B, a resveratrol tetramer, exhibited the most dramatic anti-HCV activity (EC50 = 6 nM and CC50 > 10 μM) via the disruption of the viral helicase NS3 (IC50 = 3 nM). However, its further development as an HCV drug candidate was halted due to its intrinsic drawbacks, such as poor stability, low water solubility, and restricted in vivo absorption. In order to overcome these limitations, we focused on (+)-ε-viniferin, a resveratrol dimer, as an alternative. We prepared three different versions of (+)-ε-viniferin, including one which was extracted from the grapevine root (EVF) and two which were chemically synthesized with either penta-acetylation (SVF-5Ac) or no acetylation (SVF) using a newly established synthesis method. We confirmed their anti-HCV replication activities and minimal cytotoxicity by using genotype 1b and 2a HCV replicon cells. Their anti-HCV replication action also translated into a significant reduction of viral protein expression. Anti-HCV NS3 helicase activity by EVF was also verified in vitro. Finally, we demonstrated that SVF has improved pharmacokinetic properties over vitisin B. Overall, the favorable antiviral and pharmacokinetic properties of these three versions of viniferin warrant their further study as members of a promising new class of anti-HCV therapeutics.

Chain Failure Events in Microfluidic Membrane Networks

2016 ◽  
Author(s):  
Michelle Makhoul-Mansour ◽  
Elio J. Challita ◽  
Eric C. Freeman
Keyword(s):  
Structural Integrity ◽  
Computational Prediction ◽  
Equilibrium Structure ◽  
Stimuli Responsive ◽  
Large Networks ◽  
Responsive Materials ◽  
New Class ◽  
Interfacial Energies ◽  
Membrane Networks ◽  
The Impact

Multiple lipid encased water droplets may be linked together in oil to form large networks of droplet interface bilayers thus creating a new class of stimuli-responsive materials for applications in sensing, actuation, drug delivery, and tissue engineering. While single droplet interface bilayers have been extensively studied, comparatively little is known about their interaction in large networks. One particular problem of interest is understanding the impact of the coalescence of two neighboring droplets on the overall structural integrity of the network. Here, we propose a computational modeling scheme that predicts and characterizes the mechanical properties of the multiple lipid bilayer interfaces within the droplet network upon intentional coalescence of adjacent droplets. Droplet networks with tailored architectures are synthesized with the aid of magnetic motor droplets containing a biocompatible ferrofluid. The equilibrium configuration of the droplet networks is compared to computational prediction which defines the overall stability by summing the interfacial energies. Once the networks are completed, failure in selected membranes is induced. As the targeted droplets coalesce together, the equilibrium structure of the network is altered and the remaining droplets may shift to new configurations dictated by their minimized mechanical energies.

Discovery and parallel synthesis of a new class of cathepsin k inhibitors

2001 ◽  
Vol 11 (22) ◽  
pp. 2951-2954 ◽  
Author(s):  
Roger A. Smith ◽  
Ajay Bhargava ◽  
Christopher Browe ◽  
Jinshan Chen ◽  
Jacques Dumas ◽  
...  
Keyword(s):  
Cathepsin K ◽  
Parallel Synthesis ◽  
New Class ◽  
Cathepsin K Inhibitors
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