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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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Anthelmintic drugs differ significantly from antiparasitic therapies targeting protozoa, primarily due to differences in parasite biology. Whereas most protozoal treatments act on proliferating cells, anthelmintics are typically directed against mature, nonproliferative helminths. The therapeutic approach considers the helminth's reliance on neuromuscular coordination, glucose metabolism, and microtubular integrity for survival, reproduction, and localization within the host. Most anthelmintics...
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Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
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Targeting the polyene chain represents an adjuvant strategy for optimizing polyene antifungals.

Yishan Zhang1,2,3, Xiaocong Liu1,3, Luobei Weng1,3

  • 1State Key Laboratory of Bioactive Molecules and Druggability Assessment, The First Affiliated Hospital of Jinan University Guangzhou Guangdong 510630, China.

Proceedings of the National Academy of Sciences of the United States of America
|April 21, 2026
PubMed
Summary

Researchers discovered that the polyene chain of polyene antifungals (PAs) acts as a molecular switch. Coupling PAs with adjuvants like vitamin D3 reduces kidney toxicity and enhances antifungal effectiveness.

Keywords:
amphotericin Bdrug optimizationinvasive fungal infectionpolyene antifungalsvitamin D

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Area of Science:

  • Medicinal Chemistry
  • Pharmacology
  • Mycology

Background:

  • Polyene antifungals (PAs) are crucial for treating severe fungal infections.
  • PAs cause dose-dependent nephrotoxicity due to binding to cholesterol in kidney cells, similar to their target ergosterol in fungi.

Purpose of the Study:

  • To explore the potential of the polyene chain in PAs for optimization.
  • To develop a strategy for attenuating PA-induced nephrotoxicity while enhancing antifungal efficacy.

Main Methods:

  • Investigated the polyene chain's role as a molecular switch.
  • Utilized hydrophobic coupling with clinically approved drug adjuvants.
  • Analyzed conformational rearrangements and modulated binding to membrane lipids.

Main Results:

  • The polyene chain, when coupled with adjuvants, triggers conformational changes in PAs.
  • This modulation asymmetrically affects binding to cholesterol and ergosterol, reducing kidney toxicity.
  • Vitamin D3 showed significant adjuvant activity in preclinical models and retrospective clinical data.

Conclusions:

  • Exploiting the polyene chain as a molecular switch offers a novel strategy for PA optimization.
  • Adjuvant coupling can concurrently reduce nephrotoxicity and potentiate antifungal effectiveness.
  • Vitamin D3 presents a promising adjuvant for clinical application with PAs.