Multifunctional cationic surfactants with a labile amide linker as efficient antifungal agents-mechanisms of action.

Affiliation

Paluch E(1), Szperlik J(2), Czuj T(3), Cal M(4), Lamch Ł(5), Wilk KA(5), Obłąk E(6).
Author information:
(1)Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, Tytusa Chałubińskiego 4, 50-376, Wrocław, Poland. [Email]
(2)Department of Genetic Biochemistry, Faculty of Biotechnology, University of Wroclaw, Przybyszewskiego 63, 51-148, Wroclaw, Poland.
(3)Department of Genetics, Plant Breeding and Seed Production, Faculty of Life Sciences and Technology, Wrocław University of Environmental and Life Sciences, Pl. Grunwaldzki 24A, 50-363, Wrocław, Poland.
(4)Department of Mycology and Genetics, Institute of Genetics and Microbiology, University of Wrocław, Przybyszewskiego 63/77, 51-148, Wrocław, Poland.
(5)Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wroclaw, Poland.
(6)Department Physicochemistry of Microorganisms, Institute of Genetics and Microbiology, University of Wrocław, Przybyszewskiego 63/77, 51-148, Wrocław, Poland. [Email]

Abstract

Our research aimed to expand the knowledge of relationships between the structure of multifunctional cationic dicephalic surfactants with a labile linker-N,N-bis[3,3-(dimethylamine)propyl]alkylamide dihydrochlorides and N,N-bis[3,3-(trimethylammonio)propyl]alkylamide dibromides (alkyl: n-C9H19, n-C11H23, n-C13H27, n-C15H31)-and their possible mechanism of action on fungal cells using the model organism Saccharomyces cerevisiae. General studies performed on surfactants suggest that in most cases, their main mechanism of action is based on perforation of the cell membranes and cell disruption. Experiments carried out in this work with cationic dicephalic surfactants seem to modify our understanding of this issue. It was found that the investigated compounds did not cause perforation of the cell membrane and could only interact with it, increasing its permeability. The surfactants tested can probably penetrate inside the cells, causing numerous morphological changes, and contribute to disorders in the lipid metabolism of the cell resulting in the formation of lipid droplet aggregates. This research also showed that the compounds cause severe oxidative stress within the cells studied, including increased production of superoxide anion radicals and mitochondrial oxidative stress. Dicephalic cationic surfactants due to their biodegradability do not accumulate in the environment and in the future may be used as effective antifungal compounds in industry as well as medicine, which will be environmentally friendly. KEY POINTS: • Dicephalic cationic surfactants do not induce disruption of the cell membrane. • Surfactants could infiltrate into the cells and cause accumulation of lipids. • Surfactants could cause acute oxidative stress in yeast cells. • Compounds present multimodal mechanism of action. Graphical abstract.