Losartan Plays a Fungistatic and Fungicidal Activity Against Candida albicans Biofilms: Drug Repurposing for Localized Candidosis

Assay Drug Dev Technol. 2023 May-Jun;21(4):157-165. doi: 10.1089/adt.2023.013. Epub 2023 May 25.

Abstract

Candidosis is one of the most frequent opportunistic infections and exhibits variable clinical presentations, including oral localized forms. Drugs affecting the renin-angiotensin system targets inhibit secreted aspartic proteases from Candida albicans. The objective of the study was to evaluate whether losartan has antimicrobial action against C. albicans biofilms. Biofilms were treated with losartan or aliskiren (for comparison) for 24 h. Metabolic activity of viable cells and growth inhibition of C. albicans biofilms were assessed using XTT [2,3-Bis(2-Methoxy-4-Nitro-5-Sulfophenyl)-5-[(Phenyl-Amino)Carbonyl]-2H-Tetrazolium Hydroxide] and colony-forming unit assays, respectively. In addition, the cytotoxicity of the drugs on human cells was evaluated using the AlamarBlue assay. Both drugs decreased fungal viability at all concentrations. In addition, all concentrations of losartan inhibited the growth of C. albicans biofilm, ranging from 47% to 88.5%, whereas aliskiren showed inhibition from 1 to 10 mg/mL, which ranged from 16% to 97.6%. Furthermore, at certain concentrations, these drugs maintained the viability of human cells. Losartan and aliskiren have fungistatic and fungicidal action against C. albicans biofilms and are compatible with human cells. Therefore, these antihypertensive drugs can be repurposed to interfere with the metabolism and development of Candida biofilms, which are widely associated with clinical forms of candidosis, including oral localized forms such as denture stomatitis.

Keywords: Candida albicans; aliskiren; denture stomatitis; drug repositioning; losartan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology
  • Biofilms
  • Candida albicans*
  • Drug Repositioning
  • Humans
  • Losartan* / pharmacology
  • Microbial Sensitivity Tests

Substances

  • aliskiren
  • Losartan
  • Antifungal Agents