Background

The development of new effective microbicide surfactants and the search for the structure–biological activity relationship is an important and promising problem. Surfactants containing imidazolium fragment attract attention of researchers in the field of chemotherapy, because these compounds often exhibit high antimicrobial activity. The aim of this work is to identify the newly synthesized surfactants from the viewpoint of their potential usefulness in pharmacology and medicine. For this purpose, a detailed study of antimicrobial, hemolytic and cytotoxic activity of dicationic alkylimidazolium surfactants of the m-s-m (Im) series with a variable length of a hydrocarbon tail (m = 10, 12) and a spacer fragment (s = 2, 3, 4) was carried out.

Methods

Aggregation of surfactants in solutions was estimated by tensiometry and conductivity. Antimicrobial activity was determined by the serial dilution technique. Cytotoxic effects of the test compounds on human cancer and normal cells were estimated by means of the multifunctional Cytell Cell Imaging system. Cell Apoptosis Analysis was made by flow cytometry.

Results

The test compounds show high antimicrobial activity against a wide range of test microorganisms and do not possess high hemolytic activity. Importantly, some of them display a bactericidal activity comparable to ciprofloxacin fluoroquinolone antibiotic against Gram-positive bacteria, including methicillin-resistant strains of S. aureus (MRSA). The cytotoxicity of the compounds against normal and tumor human cell lines has been tested as well, with cytotoxic effect and selectivity strongly controlled by structural factor and kind of cell line. Superior results were revealed for compound 10–4-10 (Im) in the case of HuTu 80 cell line (duodenal adenocarcinoma), for which IC₅₀ value at the level of doxorubicin and a markedly higher selectivity index (SI 7.5) were demonstrated. Flow cytometry assay shows apoptosis-inducing effect of this compound on HuTu 80 cells, through significant changes in the potential of mitochondrial membrane.

Major conclusions

Antibacterial properties are shown to be controlled by alkyl chain length, with the highest activity demonstrated by surfactants with decyl tail, with the length of the spacer fragment showing practically no effect. The results indicate that the mechanism of cytotoxic effect of the compounds can be associated with the induction of apoptosis via the mitochondrial pathway.

General significance

Selectivity against pathogenic microorganisms and low toxicity against eukaryotic cells allow considering dicationic imidazolium surfactants as new effective antimicrobial agents. At the same time, high selectivity against some cancer cell lines indicates the prospect of their using as components of new anticancer drugs.

中文翻译：

---

咪唑类表面活性剂家族的结构-活性相关性：抗菌性能和细胞毒性作用。

背景

新型有效杀菌剂表面活性剂的开发以及结构与生物活性之间的关系的研究是一个重要而有希望的问题。含有咪唑鎓片段的表面活性剂引起化学领域研究人员的关注，因为这些化合物通常表现出很高的抗菌活性。这项工作的目的是从新合成的表面活性剂在药理学和医学上的潜在用途的角度进行鉴定。为此，详细研究了具有可变长度的烃尾（m = 10、12）和间隔片段（s = 2、3）的msm（Im）系列阳离子型烷基咪唑鎓表面活性剂的抗菌，溶血和细胞毒性活性。 ，进行了4）。

方法

通过张力测定法和电导率估计溶液中表面活性剂的聚集。通过系列稀释技术确定抗菌活性。通过多功能Cytell细胞成像系统评估了测试化合物对人类癌症和正常细胞的细胞毒性作用。通过流式细胞术进行细胞凋亡分析。

结果

这些测试化合物对多种测试微生物显示出很高的抗菌活性，并且不具有很高的溶血活性。重要的是，它们中的一些对革兰氏阳性细菌，包括耐金霉素的金黄色葡萄球菌（MRSA），显示出与环丙沙星氟喹诺酮类抗生素相当的杀菌活性。还已经测试了化合物对正常和肿瘤人细胞系的细胞毒性，其细胞毒性作用和选择性受结构因素和细胞系种类的强烈控制。对于HuTu 80细胞系（十二指肠腺癌），对于化合物10–4-10（Im）表现出优异的结果，其IC ₅₀证明了阿霉素水平的最大选择性和较高的选择性指数（SI 7.5）。流式细胞仪检测表明，该化合物通过线粒体膜电位的显着变化，诱导了该化合物对HuTu 80细胞的凋亡诱导作用。

主要结论

抗菌性能显示受烷基链长度控制，具有癸基尾巴的表面活性剂显示出最高的活性，间隔片段的长度几乎没有作用。结果表明，化合物的细胞毒性作用机制可能与通过线粒体途径诱导细胞凋亡有关。

一般意义

对病原微生物的选择性和对真核细胞的低毒性使得可以考虑将咪唑类表面活性剂用作新型有效的抗菌剂。同时，对某些癌细胞系的高选择性表明了它们被用作新的抗癌药物的前景。