Novel Series of Quaternary Ammonium Surfactants Based on 2,3-Dihydro-[1,4]dioxino[2.3-b]pyridin-7-ol Ring: Synthesis, Analysis and Antimicrobial Evaluation

Background: The quaternary ammonium compounds (QAC) are the important group of chemical individuals with widespread usage in many fields of industry or science. The surface-active cationic surfactants are well known disinfection agents. Its effectivity against gram-positive, gram negative bacteria, yeasts and some viruses is already used in many preparations. On the other hand, the emergence of resistance is the cause of an increasing necessity of new substances. Methods: The series of 5-alkyl-7-hydroxy-2,3-dihydro-[1,4]clioxino[2,3-b]pyridin-5-ium bromides has been synthesized as a novel potential antimicrobial agent. Reaction of the nucleophilic substitution type has been used. The novel compounds have been tested as disinfection agents against bacteria and fungi. The microdilution broth method was utilized for antimicrobial evaluation. Standard MTT test was used for cytotoxic evaluation. Results: We have prepared 5 new compounds based on 2,3-dihydro-[1,4]clioxino[2,3-b]pyridin-7-ol with different length of lipophilic alkyl chain on the quaternary nitrogen (C-10.18). The compounds were characterized with analytical data (NMR, HRMS) and evaluated as wide spectrum antimicrobial agents against pathogenic fungal and bacterial strains. We have observed the efficacy towards microbial cells of C-12 and C-14 compounds for only several antimicrobial strains (Staphylococcus aureus, Candida krusei, Candida glabrala, Trichophylon mentagrophytes). Conclusion: We report on the preparation and characterization of a set of novel cationic surfactant-like compounds based on 2,3-dihydro-[1,4]clioxino[2,3-b]pyridin-7-ol. The novel compounds have been evaluated as wide spectrum antimicrobial agents against pathogenic fungal and bacterial strains. Only two compounds with alkyl chain C-12 and C-14 showed significant activity against microbes. So, these two compounds should be considered as the potential disinfectants with the selective effect against certain bacterial and fungal strains, not as wide spectra antimicrobial agents.