Searching for Conjugates as New Structures for Antifungal Therapies

J Med Chem. 2024 Mar 28;67(6):4298-4321. doi: 10.1021/acs.jmedchem.3c01750. Epub 2024 Mar 12.

Abstract

The progressive increase in fungal infections and the decrease in the effectiveness of current therapy explain research on new drugs. The synthesis of compounds with proven antifungal activity, favorable physicochemical and pharmacokinetic properties affecting their pharmaceutical availability and bioavailability, and limiting or eliminating side effects has become the goal of many studies. The publication describes the directions of searching for new compounds with antifungal activity, focusing on conjugates. The described modifications include, among others, azoles or amphotericin B in combination with fatty acids, polysaccharides, proteins, and synthetic polymers. The benefits of these combinations in terms of activity, mechanism of action, and bioavailability were indicated. The possibilities of creating or using nanoparticles, "umbrella" conjugates, siderophores (iron-chelating compounds), and monoclonal antibodies were also presented. Taking into account the role of vaccinations in prevention, the scope of research related to developing a vaccine protecting against fungal infections was also indicated.

Publication types

  • Review

MeSH terms

  • Amphotericin B
  • Antifungal Agents* / chemistry
  • Antifungal Agents* / pharmacology
  • Antifungal Agents* / therapeutic use
  • Azoles / therapeutic use
  • Fatty Acids
  • Humans
  • Mycoses* / drug therapy

Substances

  • Antifungal Agents
  • Amphotericin B
  • Azoles
  • Fatty Acids