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Related Concept Videos

Antifungal Agents01:15

Antifungal Agents

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 cholesterol contributes to...

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Updated: Jun 9, 2026

Broth Microdilution In Vitro Screening: An Easy and Fast Method to Detect New Antifungal Compounds
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Metal Complexes as Antifungals? From a Crowd-Sourced Compound Library to the First In Vivo Experiments.

Angelo Frei1,2, Alysha G Elliott1, Alex Kan3

  • 1Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland4072, Australia.

JACS Au
|October 31, 2022
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Summary

New metal compounds show significant antifungal activity against resistant fungal strains, offering a promising alternative to traditional drugs. Researchers identified 90 metal compounds with potent antifungal properties and low toxicity, highlighting their potential in combating fungal infections.

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Area of Science:

  • Medicinal Chemistry
  • Antimicrobial Drug Discovery
  • Inorganic Chemistry

Background:

  • The rapid spread of antifungal-resistant fungal strains necessitates the urgent development of new antifungal drugs.
  • Metal complexes are promising candidates for novel antimicrobial agents, but their antifungal potential remains largely unexplored.
  • Few antifungal drugs are currently in clinical development, increasing the risk of a future resistance crisis.

Purpose of the Study:

  • To screen a large library of metal-containing compounds for antifungal activity.
  • To identify novel metal complexes with potent antifungal properties and low toxicity.
  • To evaluate the in vivo efficacy of promising metal-based antifungal candidates.

Main Methods:

  • Screening of 1039 metal-containing compounds using the Community for Open Antimicrobial Drug Discovery (CO-ADD) platform.
  • Antifungal activity testing against *Candida* and *Cryptococcus* strains, alongside cytotoxicity and hemolytic assays.
  • In vivo toxicity assessment using the *Galleria mellonella* moth larva model and evaluation of fungal load reduction.

Main Results:

  • 20.9% of tested metal compounds exhibited antimicrobial activity, significantly higher than purely organic molecules (1.1%).
  • 90 metal compounds (8.7%) demonstrated antifungal activity without cytotoxicity or hemolytic effects at tested concentrations.
  • 21 metal complexes showed high antifungal activity (MIC ≤1.25 μM), with 11 exhibiting low toxicity in the *Galleria mellonella* model.
  • The organo-Pt(II) cyclooctadiene complex (Pt1) significantly reduced fungal load in an *in vivo* infection model.

Conclusions:

  • Metal-based compounds represent a rich source of novel antifungal agents with diverse structures and chemical properties.
  • The identified metal complexes offer promising leads for the development of new antifungal drugs to combat resistant infections.
  • Further investigation into metal complexes is crucial for addressing the growing threat of antifungal resistance and preventing a global health crisis.