Synthesis, antimicrobial activity, and toxicological evaluation of a p-coumaric acid derivative as a potential new antibacterial agent

Abstract

Aims: Bacterial infections have a profound impact on human health and require continuous development of medical treatments. They remain an important area of research due to their ability to adapt and develop resistance to available therapies. This research aims to identify an additional molecule as a potential future option for the treatment of bacterial infections.

Methods and results: 4-Chlorobenzyl p-coumarate was tested to evaluate its activity against bacterial strains in both planktonic and biofilm forms, its possible mode of action, and its toxicity through in silico, in vitro, and in vivo approaches. The molecule exhibited significant activity against Gram-positive bacteria leading to their elimination within 24 h. It induced morphological alterations on the surface and within the cells, ultimately causing cell lysis. The compound reduced bacterial biofilm, penetrated the extracellular matrix, and reached cells within the biofilm, disrupting its architecture. Toxicological assessments in predictive models were promising, showing low cytotoxic effects on human cells and no systemic toxicity.

Conclusions: 4-Chlorobenzyl p-coumarate proved to be a promising compound for proposing new investigative hypotheses considering its effect on multidrug-resistant and non-resistant Gram-positive bacteria.

Keywords: 4-chlorobenzyl p-coumarate; Gram-positive bacteria; antimicrobial potential; biofilm; mode of action; toxicity.