Project title: Discovery and development of new bioactive quaternary ammonium compounds derived from quinuclidine
Acronym: QACBioAct
Project identifier: UIP-2020-02-2356
Type of project: Installation Research Project
Funding body: Croatian science foundation (HrZZ)
Project duration: February, 01. 2021.- January, 31. 2026.
Summary
Quaternary ammonium compounds (QACs) are amphiphilic molecules with antimicrobial properties that have applications in numerous industries. Compounds such as benzalkonium chloride, cetylpyridinium chloride, and didecildimethylammonium chloride are commonly found in many antiseptics. Because QACs are amphiphilic molecules that act on the bacterial membrane, it has long been assumed that resistance to these compounds is virtually impossible. However, recent studies suggest that resistance to QACs is widespread not only because of Qac efflux pumps, but also because of another, as yet unknown, mechanism of resistance. Our previous studies have shown that quinuclidinium-containing derivatives can serve as a molecular scaffold for the development of new QACs. The aim of this study is to develop new derivatives of quinuclidinium-3-amide and their QACs and to investigate their biological activity. The mode of action of selected bioactive molecules is investigated by measuring membrane permeability to propidium iodide and analysing a bacterial sample with an atomic force microscope. To determine the possible influence of the compounds on the expression of Qac efflux pumps, their interaction with targeted macromolecules is studied by thermophoresis. The development of resistance and the expression of virulence factors in samples of bacterial cultures exposed to antimicrobial compounds will be analysed by mass spectrometry. The expected outcome of the proposed project is the discovery of new quinuclidinium-derived bioactive QACs that could have applications in the pharmaceutical, food and agricultural industries.