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Related Concept Videos

Antifungal Agents01:15

Antifungal Agents

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Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to...
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Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
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Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
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Molecular umbrella-amphotericin B conjugates.

Vaclav Janout1, Celine Bienvenu, Wiley Schell

  • 1Department of Chemistry, Lehigh University , Bethlehem, Pennsylvania 18015, United States.

Bioconjugate Chemistry
|July 29, 2014
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Summary

New molecular umbrella conjugates of amphotericin B (AmB) show improved solubility and reduced toxicity. These AmB conjugates release active antifungal agents, with varying membrane transport properties discussed for therapeutic potential.

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Area of Science:

  • Medicinal Chemistry
  • Drug Delivery Systems
  • Antifungal Agents

Background:

  • Amphotericin B (AmB) is a potent antifungal drug with significant toxicity and poor water solubility.
  • Developing safer and more effective delivery systems for AmB is crucial for treating fungal infections.

Purpose of the Study:

  • To synthesize and characterize novel tetrawalled and octawalled molecular umbrella conjugates of amphotericin B.
  • To evaluate the physicochemical properties, hemolytic activity, and drug release characteristics of these AmB conjugates.
  • To assess the membrane interaction and transport of the AmB conjugates for potential therapeutic applications.

Main Methods:

  • Synthesis of tetrawalled and octawalled molecular umbrella conjugates of AmB.
  • Assessment of water solubility, aggregation tendency, and hemolytic activity.
  • Evaluation of AmB derivative release under reducing conditions.
  • Liposomal membrane adsorption and passive transport studies.

Main Results:

  • Both conjugates demonstrated high water solubility and low aggregation.
  • Negligible hemolytic activity was observed at 100 μM for both conjugates.
  • Conjugates released active AmB derivatives under reducing conditions.
  • Octawalled conjugate showed slight liposomal membrane adsorption and passive transport, while the tetrawalled conjugate exhibited higher adsorption and lower transport.

Conclusions:

  • Molecular umbrella-AmB conjugates offer improved physicochemical properties and reduced toxicity compared to free AmB.
  • The distinct membrane interaction profiles suggest potential for targeted delivery or modified therapeutic effects.
  • These conjugates represent a promising platform for developing advanced antifungal therapies.