Gallic acid triphenylphosphonium derivatives TPP+-C10 and TPP+-C12 inhibit mitochondrial function in Candida albicans

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Victoria Valderrama1, Paula Sánchez1, Macarena Delso1

  • 1Laboratory of Applied Pharmacology for the Development of Anticancer and Antifungal Drugs, Institute for Research in Dental Sciences (ICOD), Faculty of Dentistry, University of Chile, Santiago, 8380544, Chile.

Journal of Applied Microbiology
|December 26, 2023
PubMed
Abstract

Insights

Gallic acid derivatives TPP+-C10 and TPP+-C12 show antifungal and antibiofilm properties against Candida albicans. These compounds disrupt mitochondrial function, inhibiting oxygen consumption and ATP production in the fungal cells.

Area of Science:

  • Mycology
  • Biochemistry
  • Antimicrobial Research

Background:

  • Candida albicans is a leading cause of opportunistic fungal infections.
  • Developing novel antifungal agents with unique mechanisms of action is crucial.
  • Gallic acid derivatives offer a promising scaffold for new drug discovery.

Purpose of the Study:

  • To evaluate the antifungal and antibiofilm activity of gallic acid derivatives TPP+-C10 and TPP+-C12.
  • To investigate the effects of these compounds on Candida albicans mitochondrial function.
  • To compare the efficacy of TPP+-C10 and TPP+-C12 against reference strains ATCC 90029 and ATCC 10231.

Main Methods:

  • Minimal inhibitory concentration (MIC) determined via microdilution assay.
  • Oxygen consumption measured using a Clark electrode.
  • Mitochondrial membrane potential assessed by flow cytometry with TMRE.
  • ATP levels quantified using a commercial kit.
  • Antibiofilm activity evaluated through MTT reduction assay.

Main Results:

  • Both TPP+-C10 and TPP+-C12 exhibited significant antifungal activity with MICs between 3.9-13 µM.
  • Compounds inhibited oxygen consumption, with TPP+-C12 showing a stronger effect.
  • Transmembrane potential decreased by 75%-90% in treated strains.
  • TPP+-C12 significantly reduced ATP levels by 50%.
  • Both derivatives demonstrated antibiofilm effects, TPP+-C12 being more potent.

Conclusions:

  • Gallic acid derivatives TPP+-C10 and TPP+-C12 possess potent antifungal and antibiofilm properties.
  • The mechanism of action involves the impairment of mitochondrial function in Candida albicans.
  • These compounds represent potential therapeutic agents for candidiasis.
Keywords:
Candida albicansantibiofilmantifungalbiofilmmitochondria

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