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.

中文翻译：

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具有不稳定酰胺键作为有效抗真菌剂的多功能阳离子表面活性剂-作用机理

摘要

我们的研究旨在扩展具有不稳定连接基的多功能阳离子二头表面活性剂-N，N-双[3,3-（二甲胺）丙基]烷基酰胺二盐酸盐与N，N-双[3,3- （三甲基铵）丙基]烷基酰胺二溴化物（烷基：nC ₉ H ₁₉，nC ₁₁ H ₂₃，nC ₁₃ H ₂₇，nC ₁₅ H ₃₁）以及使用模型生物酿酒酵母对真菌细胞的可能作用机理。对表面活性剂进行的常规研究表明，在大多数情况下，它们的主要作用机理是基于细胞膜的穿孔和细胞破裂。在这项工作中使用阳离子双头表面活性剂进行的实验似乎改变了我们对该问题的理解。发现所研究的化合物不会引起细胞膜穿孔，而只能与其相互作用，从而增加其渗透性。测试的表面活性剂可能会渗透到细胞内部，引起许多形态变化，并导致细胞脂质代谢紊乱，从而导致脂质液滴聚集体的形成。这项研究还表明，这些化合物会在所研究的细胞内引起严重的氧化应激，包括增加超氧阴离子自由基的产生和线粒体的氧化应激。由于双头阳离子表面活性剂的生物可降解性，它们不会在环境中累积，并且将来在工业和医学中可用作有效的抗真菌化合物，这对环境友好。

关键点

•双头阳离子表面活性剂不会引起细胞膜破裂。

•表面活性剂可能会渗入细胞并引起脂质堆积。

•表面活性剂可能在酵母细胞中引起急性氧化应激。

•化合物具有多峰作用机理。