Cationic Compounds in Antimicrobial Therapy: Structure–Activity Relationships and Emerging Technologies

Abstract

The phenomenon of antibiotic resistance is one of the most pressing challenges of our modern age. The development of multidrug-resistant (MDR) bacteria poses a serious threat to public health. Therefore, it is necessary to develop new therapeutic strategies that are a viable alternative to conventional antibiotics and, at the same time, effectively and concretely overcome their current limitations. The most promising synthetic approaches are oriented towards the use of cationic compounds, which have a physicochemical mechanism of action based on electrostatic interactions with bacterial membranes; targeting this mechanism reduces the possibility of resistance developing. Cationic compounds include antimicrobial peptides (AMPs), cationic polymers, quaternary ammonium and phosphonium salts, and gemini surfactants.

This review provides a general overview of the latest discoveries on cationic antimicrobial platforms, highlighting the structure-activity relationships, the mechanisms of action and the design strategies of these platforms showing how the molecules can be more efficient and biocompatible for humans. Natural AMPs and their synthetic mimetics have led to the development of new polymer architectures and self-assembling systems with rapid, multi-target action. Cationic polymers, on the other hand, form the basis for the development of “contact-active” antibacterial coatings and anti-biofilm materials through the modulation of their charge and hydrophobicity. Finally, gemini surfactants and cationic systems introduce structural synergy by combining antimicrobial activity, biodegradability and even possible theranostic potential.

In addition, the challenges related to environmental sustainability, biocompatibility and the integration of smart and stimulus-responsive systems are also discussed. A multidisciplinary approach among chemistry, materials science and microbiology is the key to the design of new antimicrobial agents that are effective, selective and sustainable.