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Antifungal Agents01:15

Antifungal Agents

89
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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[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction01:16

[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction

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The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.
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Fungal Group Zygomycota01:29

Fungal Group Zygomycota

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Zygomycota, previously classified as a distinct fungal group, are primarily terrestrial, saprophytic molds that play a crucial role as decomposers. Recent phylogenetic studies have revealed that these fungi are now divided into two major clades — Mucoromycota, which includes many symbiotic species, and Zoopagomycota, which primarily consists of parasitic and pathogenic fungi. These groups exhibit distinct ecological roles and reproductive strategies while sharing key structural and...
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Cycloaddition Reactions: Overview01:16

Cycloaddition Reactions: Overview

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Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
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Aryldiazonium Salts to Azo Dyes: Diazo Coupling01:11

Aryldiazonium Salts to Azo Dyes: Diazo Coupling

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The reaction of weakly electrophilic aryldiazonium (also called arenediazonium) salts with highly activated aromatic compounds leads to the formation of products with an —N=N— link, called an azo linkage. This reaction, presented in Figure 1, is known as diazo coupling and occurs without the loss of the nitrogen atoms of the aryldiazonium salt. Highly activated aromatic compounds such as phenols or arylamines favor the diazo coupling reaction. The coupling generally occurs at the...
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Updated: Apr 14, 2026

Surface Functionalization of Metal-Organic Frameworks for Improved Moisture Resistance
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Cyclopalladated Complexes With Functionalized Diphosphanes as Promising Antifungal Scaffolds.

Cláudia Malta-Luís1, Carolina Mariano1, Teresa Monteiro1

  • 1Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. República Oeiras, Lisboa, 2780-157, Portugal, unl.pt.

Bioinorganic Chemistry and Applications
|April 13, 2026
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Summary
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New palladium complexes show potent antifungal activity against drug-resistant Candida species. These novel compounds combat invasive fungal infections by inducing oxidative stress and disrupting fungal cell integrity, offering a promising new therapeutic avenue.

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Area of Science:

  • Medicinal Chemistry
  • Mycology
  • Organometallic Chemistry

Background:

  • Invasive fungal infections, particularly those caused by Candida species, represent a significant global health threat.
  • Rising antifungal resistance necessitates the development of novel therapeutic agents.
  • Palladium organometallic complexes have emerged as potential antifungal alternatives.

Purpose of the Study:

  • To synthesize and evaluate novel cyclopalladated complexes for antifungal activity.
  • To assess their efficacy against drug-resistant Candida strains and their antibiofilm properties.
  • To investigate their mechanism of action, including cellular uptake and intracellular effects.

Main Methods:

  • Synthesis of four cyclopalladated complexes (1a, 1b, 2a, 2b) derived from Schiff base-amine phosphanes.
  • Antifungal susceptibility testing against medically relevant Candida species, including resistant strains.
  • Evaluation of antibiofilm activity, cellular uptake, in vivo toxicity, and intracellular effects.
  • Analysis of structure-activity relationships.

Main Results:

  • Complexes 1b and 2b demonstrated significant antifungal activity against various Candida species.
  • These complexes effectively overcame resistance to existing antifungal drugs and exhibited antibiofilm properties.
  • Mechanistic studies revealed that 1b and 2b induce oxidative stress, lipid peroxidation, inhibit lipolysis, and disrupt vacuole integrity.
  • Structure-activity relationship analysis provided insights into the design of potent palladium-based antifungals.

Conclusions:

  • Palladium complexes represent a promising scaffold for the development of next-generation antifungal agents.
  • The synthesized complexes, particularly 1b and 2b, exhibit potent antifungal activity through multiple mechanisms.
  • Further research into palladium-based compounds could lead to novel therapeutic strategies against invasive fungal infections.