Hemolytic and Antimicrobial Activities of a Series of Cationic Amphiphilic Copolymers Comprised of Same Centered Comonomers with Thiazole Moieties and Polyethylene Glycol Derivatives

Abstract

A series of well-defined antimicrobial polymers composed of comonomers bearing thiazole ring (2-(((2-(4-methylthiazol-5-yl)ethoxy)carbonyl)oxy)ethyl methacrylate monomer (MTZ)) and non-hemotoxic poly(ethylene glycol) side chains (poly(ethylene glycol) methyl ether methacrylate (PEGMA)) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. By post-polymerization functionalization strategy, polymers were quaternized with either butyl or octyl iodides to result in cationic amphiphilic copolymers incorporating thiazolium groups, thus with variable hydrophobic/hydrophilic balance associated to the length of the alkylating agent. Likewise, the molar percentage of PEGMA was modulated in the copolymers, also affecting the amphiphilicity. The antimicrobial activities of these cationic polymers were determined against Gram-positive and Gram-negative bacteria and fungi. Minimum inhibitory concentration (MIC) was found to be dependent on both length of the alkyl hydrophobic chain and the content of PEGMA in the copolymers. More hydrophobic octylated copolymers were found to be more effective against all tested microorganisms. The incorporation of non-ionic hydrophilic units, PEGMA, reduces the hydrophobicity of the system and the activity is markedly reduced. This effect is dramatic in the case of butylated copolymers, in which the hydrophobic/hydrophilic balance is highly affected. The hemolytic properties of polymers analyzed against human red blood cells were greatly affected by the hydrophobic/hydrophilic balance of the copolymers and the content of PEGMA, which drastically reduces the hemotoxicity. The copolymers containing longer hydrophobic chain, octyl, are much more hemotoxic than their corresponding butylated copolymers.

Biobased polymers derived from itaconic acid bearing clickable groups with potent antibacterial activity and negligible hemolytic activity

“…Although this better behavior against Gram-positive bacteria was also revealed in our previous investigations with cationic methacrylic polymers bearing thiazole and triazole groups, such polymers also pre-sented significant activity against Gram-negative bacteria. 22,25,30 In the current work, the polymers derived from IA present four positive charges per monomeric unit, thus, a very high positive charge. In this case, with a high charge density, even when high content of the hydrophobic monomer DMI is used, the activity is almost nullified against Gram-negative bacteria.…”

“…Hemolysis studies were carried out as described previously. 24,25 Fresh human blood was collected from healthy donors and used within the same day. Blood was drawn directly into the blood collecting tubes containing EDTA to prevent coagulation.…”

Antibacterial Amphiphilic Copolymers of Dimethylamino Ethyl Methacrylate and Methyl Methacrylate to Control Biofilm Adhesion for Antifouling Applications

“…They studied antibacterial effects of linear and cyclic monomers of cyclic poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) based copolymers with various components by the intra-chain click cyclization of α-alkyne-ω-azido via atom transfer radical polymerization [ 23 ]. In another study of amphiphilic polymers of thiazole ring 2-(2-(4-methylthiazol-5-yl)ethoxy)carbonyl)oxy)ethyl methacrylate monomer (MTZ) and non-hemotoxic poly(ethylene glycol) side chains (poly(ethylene glycol) methyl ether methacrylate (PEGMA) observed that longer hydrophobic chain, octyl were much more hemotoxic than their corresponding butylated copolymers [ 24 ].…”

Imidazole and Imidazolium Antibacterial Drugs Derived from Amino Acids

“…Moreover, pharmaceutical research, manufacture, and regulation are enhancing the development of solid active ingredients, delivered as powders or tablets; however, many solid drugs which perform well in in vitro evaluation remain too insoluble for the body to absorb [ 8 , 9 ]. Most of the bioactive agents sold for pharmaceutical or food industries are salts [ 10 , 11 ], and in this context, ionic liquids (ILs) represent a promising class of drug candidates whose physicochemical and pharmaceutical properties can be easily tuned [ 12 , 13 , 14 , 15 , 16 , 17 ]. In this regard, the imidazolium skeleton can be transformed into ionic liquids with promisingly potent pharmacological properties [ 18 , 19 , 20 , 21 ].…”