The structure – Activity correlation in the family of dicationic imidazolium surfactants: Antimicrobial properties and cytotoxic effect

• Published in: Biochimica et biophysica acta. General subjects Vol. 1864; no. 12; p. 129728
• Main Authors: Voloshina, Alexandra D., Gumerova, Syumbelya K., Sapunova, Аnastasiia S., Kulik, Natalia V., Mirgorodskaya, Alla B., Kotenko, Alla A., Prokopyeva, Tatiana M., Mikhailov, Vasilii A., Zakharova, Lucia Ya, Sinyashin, Oleg G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2020
• Subjects: adenocarcinoma; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; antibacterial properties; Antimicrobial activity; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Bacteria - drug effects; Bacterial Infections - drug therapy; Cell Line; Cell Line, Tumor; ciprofloxacin; Cytotoxicity; Dicationic imidazolium surfactants; disinfectants; doxorubicin; drug therapy; flow cytometry; Fungi - drug effects; Gram-Positive Bacteria - drug effects; Hemolysis; Humans; imidazoles; Imidazoles - chemistry; Imidazoles - pharmacology; medicine; methicillin-resistant Staphylococcus aureus; Microbial Sensitivity Tests; mitochondria; Mycoses - drug therapy; neoplasm cells; Neoplasms - drug therapy; pharmacology; Resistance; Structure-Activity Relationship; Surface-Active Agents - chemistry; Surface-Active Agents - pharmacology; Hemolysis; Resistance; Dicationic imidazolium surfactants; Cytotoxicity; Antimicrobial activity; Apoptosis
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2020.129728

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. 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. 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. 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. 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. •Antimicrobial, hemolytic, cytotoxic activities of m-s-m(Im) surfactants were studied.•The highest antimicrobial activity was observed for surfactants of 10-s-10(Im) series.•10-s-10 (Im) show high bactericidal activity against methicillin-resistant strains.•10-4-10 (Im) demonstrates IC50 at the level of doxorubicin (HuTu 80 cell line).•Сytotoxic effect is associated with induction of apoptosis via mitochondrial pathway