N-alkylimidazolium Salts Functionalized with p-Coumaric and Cinnamic Acid: A Study of Their Antimicrobial and Antibiofilm Effects

Abstract

The bacterial resistance to antibiotics has compromised the therapies used for bacterial infections. Nowadays, many strategies are being carried out to address this problem. Among them, the use of natural compounds like cinnamic and p-coumaric acids stands out. Nevertheless, their utilization is limited because of their unfavorable physicochemical properties. Due to the lack of new therapeutic alternatives for bacterial infections, novel strategies have emerged, such as the use of ionic liquids; given that they can show a broad spectrum of antibacterial activity, this is why we herein report the antibacterial and antibiofilm activity of a series of N-alkylimidazolium salts functionalized with p-coumaric and cinnamic acids. The results from this study showed better antibacterial activity against Gram-positive bacteria, with a predominance of the salts derived from coumaric acid and a correlation with the chain length. Additionally, a lower efficacy was observed in the inhibition of biofilm formation, highlighting the antibiofilm activity against Staphylococcus aureus, which decreased the production of the biofilm by 52% over the control. In conclusion, we suggest that the salts derived from p-coumaric acid are good alternatives as antibacterial compounds. Meanwhile, the salt derived from cinnamic acid could be a good alternative as an antibiofilm compound.

Hydroxycinnamic Acids and Derivatives Formulations for Skin Damages and Disorders: A Review

“…In addition to their applications in the food industry, CinAc and its derivatives have been widely explored in the pharmaceutical and biomedical field, displaying a broad spectrum of actions, such as anti-bacterial [ 32 ], anti-fungal, anti-cancer, anti-inflammatory, neuroprotective, cardioprotective, and anti-diabetic activities. In particular, considering the basic structure of CinAc, the benzene ring and the acrylic acid group allow various chemical modifications which lead to several CinAc synthetic derivatives, with enhanced bioactive properties, amplified electron-withdrawn ability (needed for an efficient free radical scavenging), modified lipophilicity, and ameliorated absorption and biodistribution [ 33 , 34 ].…”

Biofilm control by ionic liquids

“…More recently, innovative N-alkylimidazolium ILs functionalized with plant secondary metabolites (phytochemicals) of the shikimate pathway, such as p-coumaric and cinnamic acids, and with different chain lengths, were developed. They demonstrated antibiofilm activity against Gramnegative and Gram-positive bacteria, with the strongest potency being found for derivatives that contained alkyl chains of eight and ten carbons [74]. 1-Cinnamoyl-3-octyl-1H-imidazol-3-ium bromide was revealed to be the strongest IL [74].…”

“…They demonstrated antibiofilm activity against Gramnegative and Gram-positive bacteria, with the strongest potency being found for derivatives that contained alkyl chains of eight and ten carbons [74]. 1-Cinnamoyl-3-octyl-1H-imidazol-3-ium bromide was revealed to be the strongest IL [74]. The same strategy has been implemented using amino acids as modifiers of the imidazolium cation [70].…”

Ionic Systems and Nanomaterials as Antiseptic and Disinfectant Agents for Surface Applications: A Review

“…In the case of Gram-negative Escherichia and Raoultella genus, salts containing amino acid anions showed lower activity on microorganisms, being 2 to 10 times less active than the antimicrobial activity of benzalkonium chloride. In 2019, Forero-Doria et al [28] investigated the potential of imidazole based ILs with p-coumaric and cinnamic acid as alternative strategies to tackle bacterial resistance to antibiotics. Researchers synthesized N-alkylimidazolium salts in an elongating alkyl chain and tested antimicrobial and antibiofilm activity against Gram-positive and Gram-negative bacteria.…”