# Antifungal Activity of Four Medium-Chain Fatty Acids and γ-Undecalactone Against Candida albicans

## TL;DR

This study shows that γ-undecalactone effectively fights Candida albicans at specific concentrations without harming red blood cells.

## Contribution

The novel finding is that γ-undecalactone has antifungal activity against C. albicans with low cytotoxicity.

## Key findings

- γ-undecalactone inhibits C. albicans growth at 112.5 µg/mL (MIC) and kills it at 225 µg/mL (MFC).
- Antifungal activity increases with longer carbon chains in medium-chain fatty acids.
- γ-undecalactone does not cause hemolysis at MFC concentrations.

## Abstract

In this paper, the antifungal activity of medium-chain fatty acids with 8 to 11 carbon atoms in their chemical structures, medium-chain fatty acid lactones, and a partially fluorinated medium-chain fatty acid was determined. As the length of the alkyl chain increased in medium-chain fatty acids with 8 to 11 carbon atoms, the MIC and MFC became smaller, with increased antifungal activity (octanoic acid, 225 µg/mL(MIC), 450 µg/mL (MFC); nonanoic acid, 225 µg/mL (MIC), 450 µg/mL (MFC); decanoic acid, 112.5 µg/mL (MIC), 225 µg/mL (MFC); undecanoic acid, 112.5 µg/mL (MIC), 225 µg/mL (MFC)), whereas the antifungal activity of γ-undecalactone, in which the carboxyl group of the medium-chain fatty acid with 11 carbon atoms was converted to a five-membered lactone ring, also had antifungal activity (γ-undecalactone, 112.5 µg/mL (MIC), 225 µg/mL (MFC)). The antifungal activity of the partially fluorinated fatty acid with 11 carbon atoms and δ-undecalactone was not observed and their MICs were not evaluated in this study. The equation derived through multiple regression analysis revealed that the polarizability value was significantly related to the MICs or MFCs of fatty acids containing 8 to 11 carbon atoms and γ-undecalactone (R2 = 0.78, p < 0.05). C. albicans cultured at 37 °C with γ-undecalactone at the MIC formed hyphae or biofilms, which were observed using scanning electron microscopy in this study. Dead C. albicans were observed when cultured at 37 °C with γ-undecalactone at the MFC, indicating that in order to demonstrate complete killing, C. albicans must be killed at or above the MFC of γ-undecalactone when cultured at 37 °C. γ-undecalactone exhibited no hemolytic activity at the MFC, similar to negative controls. Our results show that γ-undecalactone has an antifungal effect against C. albicans over the MFC, without hemodialysis as the observed cytotoxicity.