Cyclization and unsaturation rather than isomerisation of side chains govern the selective antibacterial activity of cationic-amphiphilic polymers

Abstract

Membrane-active agents represent a promising alternative to overcome antibiotic resistance. Here, we report cationic-amphiphilic polymers with variations in the side chain architecture such as cyclization, isomerization and unsaturation that resulted in potent antibacterial activity and low mammalian cell toxicity with a membrane-active mode of action.

Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria

“…We have reported the synthesis and characterization of cationic-amphiphilic macromolecules based on poly(isobutylene- alt - N -alkyl maleimide) backbone previously [ 30 – 32 ]. The detailed synthetic protocols and complete characterization have been reported previously [ 30 – 32 ].…”

“…We have reported the synthesis and characterization of cationic-amphiphilic macromolecules based on poly(isobutylene- alt - N -alkyl maleimide) backbone previously [ 30 – 32 ]. The detailed synthetic protocols and complete characterization have been reported previously [ 30 – 32 ]. These macromolecules selectively displayed potent antibacterial efficacy against actively growing planktonic bacteria with minimal toxicity to mammalian cells with membrane-active mode of action as described earlier [ 30 – 32 ].…”

“…Synthesis and characterization of cationic amphiphilic macromolecules was as described previously [ 29 – 32 ]. Briefly, to a solution of 0.5 g of Poly(isobutylene-alt-N-(N' , N'-dimethylaminopropyl)-maleimide) (PIBMI) [ 29 – 32 ] in 20 mL of dry DMF/dry CHCl 3 (1:1), 2 equivalents (with respect to the monomer weight of PIBMI) of N -alkyl-1-bromoethanamide [ 29 – 32 ] was added and stirred at 75°C for 96 h in a screw top pressure tube. The solution was cooled, precipitated with 40 mL of diethyl ether and filtered.…”

Biomimetic antimicrobial polymers: recent advances in molecular design

“…Related advances have been made by the Haldar group using alternating copolymers of maleimide and isobutylene. 128 These findings suggest that alternating sequence is a prudent and perhaps under-appreciated design strategy. Very recently, Perrier and co-workers undertook a detailed study of sequence control in antimicrobial poly(acrylamide)s bearing hydrophobic isopropyl and cationic aminoethyl side chains.…”

Antibacterial Activity of Polymers: Discussions on the Nature of Amphiphilic Balance

“…[6] Haldar similarly showed that cyclization and unsaturation of the hydrophobic groups in amphiphilic polymers are important determinants of bioactivity. [7] Removing pendant hydrophobic groups altogether,L ienkamp and co-workers recently reported polyoxanorbornenes with pendant zwitterionic groups where the backbone imparted hydrophobicity in- stead. [8] Similarly,P alermo and co-workers reported selfimmolative poly(benzyl ether)s with pendant oligo(ethylene glycol) and thioether-linked primary amines,w hich are both nominally hydrophilic, whereas the backbone is intensely hydrophobic.…”