Phytochemicals and quaternary phosphonium ionic liquids: Connecting the dots to develop a new class of antimicrobial agents

Efficacy of Novel Quaternary Ammonium and Phosphonium Salts Differing in Cation Type and Alkyl Chain Length against Antibiotic-Resistant Staphylococcus aureus

“…Such a medical insurgence could compromise the efficacy of currently available antibiotics, posing a major threat to public health [ 4 ]. According to a World Health Organization (WHO) report, at least 700,000 people globally die each year from antibiotic-resistant bacterial infections [ 5 , 6 ]. In 2019, the United States reported more than 2.8 million cases of antibiotic-resistant bacterial infections, resulting in over 35,000 deaths [ 5 ], while Europe witnessed about 33,000 annual deaths attributed to antibiotic-resistant infections [ 7 ].…”

“…Quaternary heteronium salts (QHSs), such as quaternary ammonium and phosphonium compounds, present a promising avenue for discovering new antibiotics to counter antibacterial resistance [ 6 , 12 , 13 , 14 , 15 ]. Since the 1930s, quaternary ammonium salts (QASs) have been integral components of various antiseptics and disinfectants [ 6 , 16 , 17 , 18 , 19 ], finding applications in household, agriculture, medicine, and industry [ 16 , 17 , 19 ].…”

“…Quaternary heteronium salts (QHSs), such as quaternary ammonium and phosphonium compounds, present a promising avenue for discovering new antibiotics to counter antibacterial resistance [ 6 , 12 , 13 , 14 , 15 ]. Since the 1930s, quaternary ammonium salts (QASs) have been integral components of various antiseptics and disinfectants [ 6 , 16 , 17 , 18 , 19 ], finding applications in household, agriculture, medicine, and industry [ 16 , 17 , 19 ]. The structure of QASs comprises a positively charged nitrogen atom (head) linked through four bonds to alkyl or aryl chains (tails) with varying numbers of carbon atoms [ 16 , 17 , 18 ].…”

“…Depending on their structure, they exhibit antimicrobial activity against Gram-positive bacteria, fungi, and enveloped viruses [ 16 ]. Despite extensive research, the precise mechanism of action of QASs is not yet fully elucidated [ 6 , 16 , 20 ]; however, it is widely acknowledged that they interact with cell membranes [ 16 , 21 ]. Selectivity is thought to rely on differences between pathogenic and mammalian membranes, with the former abundant in negatively charged components and the latter in zwitterionic ones.…”

“…In contrast, mammalian cell membranes, predominantly composed of zwitterionic lipids (e.g., phosphatidylcholine), demonstrate diminished interactions with QASs [ 21 ]. Additionally, some studies indicate a correlation between membrane activity and the hydrophobicity of the active molecule, as well as the density of the cationic charge [ 6 , 12 ].…”