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Amido-quinuclidine based QACs as a new soft antimicrobial agents susceptible to protease degradation

Quaternary ammonium compounds (QACs) are biologically active amphiphiles displaying potent antimicrobial properties (M.D. Joyce et al., 2015). Given the alarming number of QACs resistant environmental isolates, the aim of further QACs research is to synthetise soft QACs variants more prone to either spontanious or enzymatic degradation. Our previous studies on QACs have shown that quinuclidine is a good starting structure for quaternization and that its derivatives have potent antimicrobial activity (Bazina et al., 2019). It is also known that amide bond is susceptible to peptidase degradation. This fact implies that compounds containing such bond could be degraded more easily in the environment by enzymatic decomposition. For these reasons, we were set to synthesize new amido-quinuclidine derivatives with long alkyl chains to yield biologically active and more environmental friendly QACs variants. A series of six new compounds QAd12, MeQAd12, AlyQAd12, QAd14, MeQAd14 and AlyQAd14 were synthesized and analyzed for their antimicrobial activity using a panel of pahtogenic bacteria and fungus. All compounds display good antimicrobial potential at concentrations in μM range. To investigate if those compounds are succesfully degraded by cellular peptidases, enzymatic digestion of compounds using cell lysates will be preformed. This finding might shed light on new potential mechanism for production of environmental friendly QACs.

synthesis, quaternary ammonium compounds (QACs), amide bond, biological activity

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