41341-55-3Relevant academic research and scientific papers
Directing Drugs to Bugs: Antibiotic-Carbohydrate Conjugates Targeting Biofilm-Associated Lectins of Pseudomonas aeruginosa
Meiers, Joscha,Zahorska, Eva,R?hrig, Teresa,Hauck, Dirk,Wagner, Stefanie,Titz, Alexander
, p. 11707 - 11724 (2020/12/02)
Chronic infections by Pseudomonas aeruginosa are characterized by biofilm formation, which effectively enhances resistance toward antibiotics. Biofilm-specific antibiotic delivery could locally increase drug concentration to break antimicrobial resistance and reduce the drug's peripheral side effects. Two extracellular P. aeruginosa lectins, LecA and LecB, are essential structural components for biofilm formation and thus render a possible anchor for biofilm-targeted drug delivery. The standard-of-care drug ciprofloxacin suffers from severe systemic side effects and was therefore chosen for this approach. We synthesized several ciprofloxacin-carbohydrate conjugates and established a structure-activity relationship. Conjugation of ciprofloxacin to lectin probes enabled biofilm accumulation in vitro, reduced the antibiotic's cytotoxicity, but also reduced its antibiotic activity against planktonic cells due to a reduced cell permeability and on target activity. This work defines the starting point for new biofilm/lectin-targeted drugs to modulate antibiotic properties and ultimately break antimicrobial resistance.
Development of photoswitchable inhibitors for β-galactosidase
Rustler, Karin,Mickert, Matthias J.,Nazet, Julian,Merkl, Rainer,Gorris, Hans H.,K?nig, Burkhard
, p. 7430 - 7437 (2018/10/24)
Azobenzenes are of particular interest as a photochromic scaffold for biological applications because of their high fatigue resistance, their large geometrical change between extended (trans) and bent (cis) isomer, and their diverse synthetic accessibility. Despite their wide-spread use, there is no reported photochromic inhibitor of the well-investigated enzyme β-galactosidase, which plays an important role for biochemistry and single molecule studies. Herein, we report the synthesis of photochromic competitive β-galactosidase inhibitors based on the molecular structure of 2-phenylethyl β-d-thiogalactoside (PETG) and 1-amino-1-deoxy-β-d-galactose (β-d-galactosylamine). The thermally highly stable PETG-based azobenzenes show excellent photochromic properties in polar solvents and moderate to high photostationary states (PSS). The optimized compound 37 is a strong competitive inhibitior of β-galactosidase from Escherichia coli and its inhibition constant (Ki) changes between 60 nM and 290 nM upon irradiation with light. Additional docking experiments supported the observed structure-activity relationship.
Application of halide molten salts as novel reaction media for O-glycosidic bond formation
Kumar, Vineet,Talisman, Ian Jamie,Malhotra, Sanjay V.
supporting information; experimental part, p. 3377 - 3381 (2010/08/19)
In this study we have explored the application of halide molten salts as reaction media for O-glycosidic bond formation under basic conditions and mild heating. Eighteen different room-temperature ionic liquids and molten salts, representing four different classes of cations (i.e. imidazolium, pyridinium, pyrrolidinium and ammonium), were screened in the glycosidation reaction of p-nitrophenol with aceto-bromo-α-D-galactose. 1-Butyl-4-methylimidazolium chloride (BMIM·Cl) gave the best results and was applied in the reactions of other phenolic substrates to give the products with up to 80% yields. All the reactions were highly selective to give the β-anomers, and the molten salt BMIM·Cl could easily be reused with no apparent loss in activity.
Solvent-free synthesis of thioglycosides by ball milling
Ramrao Patil, Premanand,Ravindranathan Kartha
experimental part, p. 953 - 956 (2010/04/23)
Thioglycosides have been prepared in excellent yields by three different routes from a range of readily available glycosyl halides under solvent-free conditions employing a planetary ball mill.
Aryl O- and S-galactosides and lactosides as specific inhibitors of human galectins-1 and -3: Role of electrostatic potential at O-3
Giguere, Denis,Sato, Sachiko,St-Pierre, Christian,Sirois, Suzanne,Roy, Rene
, p. 1668 - 1672 (2007/10/03)
Phase transfer catalyzed reaction was used for the high yielding synthesis of aryl 1-thio-β-d-galacto- and lacto-pyranosides carrying a panel of substituents on the phenyl groups. Best galectin-1 inhibitors were simple p-nitrophenyl thiogalactoside 5a for
Facile synthesis of 1,2-trans-nitrophenyl-1-thioglycopyranosides
Driguez,Szeja
, p. 1413 - 1414 (2007/10/02)
1,2-trans-2-Nitro-, 4-nitro- and 2,4-dinitrophenyl-1-thioglycopyranosides were synthesized in high yield by condensation of per-O-acetyl-1-thioglucose with the appropriate nitro- or dinitrofluorobenzene in the presence of potassium carbonate. The pseudothiourea precursor was also used under these coupling conditions. 1,2-trans-4-Nitrophenyl-1-thioglycosides derived from β-D-galactose, β-D-xylose, α-L-arabinose and maltose were also obtained in good yield.
Mild stereoselective syntheses of thioglycosides under PTC conditions and their use as active and latent glycosyl donors
Cao,Meunier,Andersson,Letellier,Roy
, p. 2303 - 2312 (2007/10/02)
Mild and stereoselective arylthio glycoside syntheses were accomplished by inversion of configuration of glycosyl halides under phase transfer catalyzed conditions. Under such conditions, aryl α-thiosialosides having electron donating and withdrawing subs
