Design, Synthesis, and Evaluation of Novel Fluoroquinolone−Aminoglycoside Hybrid Antibiotics

2009 ◽  
Vol 52 (8) ◽  
pp. 2243-2254 ◽  
Author(s):  
Varvara Pokrovskaya ◽  
Valery Belakhov ◽  
Mariana Hainrichson ◽  
Sima Yaron ◽  
Timor Baasov
Keyword(s):  
Design Synthesis ◽  
Hybrid Antibiotics

scholarly journals Semisynthetic Analogs of the Antibiotic Fidaxomicin – Design, Synthesis, and Biological Evaluation

2020 ◽  
Author(s):  
Andrea Dorst ◽  
Regina Berg ◽  
Christoph Gertzen ◽  
Daniel Schäfle ◽  
katja zerbe ◽  
...  
Keyword(s):  
Structural Design ◽  
Water Solubility ◽  
Biological Evaluation ◽  
Protecting Group ◽  
Design Synthesis ◽  
Gram Positive Bacteria ◽  
Excellent Activity ◽  
One Step ◽  
Hybrid Antibiotics ◽  
Synthesis And Biological Evaluation

<p>The glycoslated macrocyclic antibiotic fidaxomicin (1, tiacumicin B, lipiarmycin A3) displays good to excellent activity against Gram-positive bacteria and was approved for the treatment of Clostridium difficile infections (CDI). Main limitations of the compound include low water solubility, which impacts further clinical use. We report on the synthesis of new fidaxomicin derivatives based on structural design and utilizing an operationally simple one-step protecting group-free preparative approach from the natural product. An increase in solubility of up to 25-fold with largely retained activity was observed. Furthermore, hybrid antibiotics were prepared that show improved antibiotic activities</p>

scholarly journals Semisynthetic Analogs of the Antibiotic Fidaxomicin – Design, Synthesis, and Biological Evaluation

2020 ◽  
Author(s):  
Andrea Dorst ◽  
Regina Berg ◽  
Christoph Gertzen ◽  
Daniel Schäfle ◽  
katja zerbe ◽  
...  
Keyword(s):  
Structural Design ◽  
Water Solubility ◽  
Biological Evaluation ◽  
Protecting Group ◽  
Design Synthesis ◽  
Gram Positive Bacteria ◽  
Excellent Activity ◽  
One Step ◽  
Hybrid Antibiotics ◽  
Synthesis And Biological Evaluation

<p>The glycoslated macrocyclic antibiotic fidaxomicin (1, tiacumicin B, lipiarmycin A3) displays good to excellent activity against Gram-positive bacteria and was approved for the treatment of Clostridium difficile infections (CDI). Main limitations of the compound include low water solubility, which impacts further clinical use. We report on the synthesis of new fidaxomicin derivatives based on structural design and utilizing an operationally simple one-step protecting group-free preparative approach from the natural product. An increase in solubility of up to 25-fold with largely retained activity was observed. Furthermore, hybrid antibiotics were prepared that show improved antibiotic activities</p>

scholarly journals Design, synthesis and microbiological evaluation of ampicillin–tetramic acid hybrid antibiotics

2016 ◽  
Vol 70 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Philip T Cherian ◽  
Aditi Deshpande ◽  
Martin N Cheramie ◽  
David F Bruhn ◽  
Julian G Hurdle ◽  
...  
Keyword(s):  
Tetramic Acid ◽  
Design Synthesis ◽  
Hybrid Antibiotics

Self-Assembly of Hydrogels From Elastin-Mimetic Block Copolymers

2002 ◽  
Vol 724 ◽  
Author(s):  
Elizabeth R. Wright ◽  
R. Andrew McMillan ◽  
Alan Cooper ◽  
Robert P. Apkarian ◽  
Vincent P. Conticello
Keyword(s):  
Block Copolymers ◽  
Self Assembly ◽  
Triblock Copolymers ◽  
Variable Temperature ◽  
Inverse Temperature ◽  
Temperature Transition ◽  
Scanning Calorimetry ◽  
Design Synthesis ◽  
Inverse Temperature Transition ◽  
Functional Biomaterials

AbstractTriblock copolymers have traditionally been synthesized with conventional organic components. However, triblock copolymers could be synthesized by the incorporation of two incompatible protein-based polymers. The polypeptides would differ in their hydrophobicity and confer unique physiochemical properties to the resultant materials. One protein-based polymer, based on a sequence of native elastin, that has been utilized in the synthesis of biomaterials is poly (Valine-Proline-Glycine-ValineGlycine) or poly(VPGVG) [1]. This polypeptide has been shown to have an inverse temperature transition that can be adjusted by non-conservative amino acid substitutions in the fourth position [2]. By combining polypeptide blocks with different inverse temperature transition values due to hydrophobicity differences, we expect to produce amphiphilic polypeptides capable of self-assembly into hydrogels. Our research examines the design, synthesis and characterization of elastin-mimetic block copolymers as functional biomaterials. The methods that are used for the characterization include variable temperature 1D and 2D High-Resolution-NMR, cryo-High Resolutions Scanning Electron Microscopy and Differential Scanning Calorimetry.

Discovery of Antibacterial Agents Inhibiting the Energy-Coupling Factor (ECF) Transporters by Structure-Based Virtual Screening

2020 ◽  
Author(s):  
Eleonora Diamanti ◽  
Inda Setyawati ◽  
Spyridon Bousis ◽  
leticia mojas ◽  
lotteke Swier ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Energy Coupling ◽  
Coupling Factor ◽  
Design Synthesis ◽  
Screening Design ◽  
Starting Point ◽  
Wide Range ◽  
Vitamin Uptake

Here, we report on the virtual screening, design, synthesis and structure–activity relationships (SARs) of the first class of selective, antibacterial agents against the energy-coupling factor (ECF) transporters. The ECF transporters are a family of transmembrane proteins involved in the uptake of vitamins in a wide range of bacteria. Inhibition of the activity of these proteins could reduce the viability of pathogens that depend on vitamin uptake. Because of their central role in the metabolism of bacteria and their absence in humans, ECF transporters are novel potential antimicrobial targets to tackle infection. The hit compound’s metabolic and plasma stability, the potency (20, MIC Streptococcus pneumoniae = 2 µg/mL), the absence of cytotoxicity and a lack of resistance development under the conditions tested here suggest that this scaffold may represent a promising starting point for the development of novel antimicrobial agents with an unprecedented mechanism of action.<br>

New Molecular Scaffolds for Fluorescent Voltage Indicators

2018 ◽  
Author(s):  
Steven Boggess ◽  
Shivaani Gandhi ◽  
Brian Siemons ◽  
Nathaniel Huebsch ◽  
Kevin Healy ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Action Potentials ◽  
Induced Pluripotent Stem Cell ◽  
Molecular Wire ◽  
Voltage Sensing ◽  
Design Synthesis ◽  
Cardiac Action ◽  
Action Potential Waveform ◽  
Induced Pluripotent ◽  
Voltage Sensing Domain

<div> <p>The ability to non-invasively monitor membrane potential dynamics in excitable cells like neurons and cardiomyocytes promises to revolutionize our understanding of the physiology and pathology of the brain and heart. Here, we report the design, synthesis, and application of a new class of fluorescent voltage indicator that makes use of a fluorene-based molecular wire as a voltage sensing domain to provide fast and sensitive measurements of membrane potential in both mammalian neurons and human-derived cardiomyocytes. We show that the best of the new probes, fluorene VoltageFluor 2 (fVF 2) readily reports on action potentials in mammalian neurons, detects perturbations to cardiac action potential waveform in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes, shows a substantial decrease in phototoxicity compared to existing molecular wire-based indicators, and can monitor cardiac action potentials for extended periods of time. Together, our results demonstrate the generalizability of a molecular wire approach to voltage sensing and highlights the utility of fVF 2 for interrogating membrane potential dynamics.</p> </div>

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