Bacterial infections and antibiotic resistance, mainly by Gram-negative pathogens, have become a global healthcare crisis that is in urgent need of addressing. Numerous antimicrobial polymers had been developed over the past few decades. However, many of them suffer higher cytotoxicity against mammalian cells and are ineffective particularly against multidrug-resistant Gram-negative bacteria. As such, the development of new antimicrobial agents with enhanced activity and lower cytotoxicity are needed to prevent the inception of a post-antibiotic era. We used bile acid derivatives to prepare antimicrobial polymers. Bile acids are cholesterol-derived amphiphilic steroid acids produced in mammals and other vertebrates. We have synthesized multiple cationic charge-containing facial amphiphilic polymers via post-polymerization modification based on derivatives (lithocholic, deoxycholic, and cholic acid) of a multicyclic terpenoid, a bile acid. These derivatives bear single, double, and triple quaternary ammoniums head groups respectively. All these polymers surprisingly showed potent activity against Gram-negative bacteria. Cholic acid-based cationic polymers exhibited higher antimicrobial activity than that of other two derivatives. The enhanced activity of bile acid derivatives against Gram-negative bacteria is due to the presence of facially oriented hydrophilic cationic head groups and hydrophobicity of the multicyclic fused rings, which provide higher interactions with bacterial cells.

Facial amphiphilic antimicrobial polymers using multicyclic bile acids

256th National Meeting (2018)

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