Nitrogen- and Oxygen-Containing Heterocyclic Compounds as Antimicrobial, Antibiofilm, and Antivirulence Agents: A Review

Abstract

The rapid emergence of antimicrobial resistance (AMR) and multidrug-resistant (MDR) pathogens have become a critical global health challenge, necessitating the development of alternative therapeutic strategies beyond conventional antibiotics. This review critically evaluates recent advances (2018–2024) in nitrogen- and oxygen-containing heterocyclic compounds, including imidazolidine derivatives and quinoline–triazole hybrids, as promising antimicrobial, antibiofilm, and antivirulence agents. Evidence from recent studies indicates that these heterocyclic scaffolds exhibit broad-spectrum antimicrobial activity against clinically relevant pathogens such as Staphylococcus aureus and Escherichia coli, with several compounds demonstrating significant biofilm inhibition (>60%) and quorum sensing suppression.
In addition to direct antimicrobial effects, these compounds effectively disrupt microbial virulence pathways without imposing strong selective pressure, thereby offering a sustainable approach to resistance management. Structure–activity relationship (SAR) studies highlight the critical role of substitution patterns, lipophilicity, and hybrid pharmacophore design in modulating biological activity and target interactions. Furthermore, computational approaches, including molecular docking, molecular dynamics simulations, and in silico ADME predictions, have provided mechanistic insights into binding affinities, structural stability, and drug-likeness profiles, thereby accelerating lead optimization.
Notably, hybrid pharmacophore strategies, particularly quinoline–triazole conjugates, have demonstrated enhanced antimicrobial potency and improved pharmacokinetic properties compared to individual scaffolds. Despite promising in vitro outcomes, challenges related to toxicity, pharmacokinetics, and clinical translation remain. Overall, this review underscores the therapeutic potential of heterocyclic compounds as next-generation antimicrobial agents and emphasizes the need for integrated experimental and computational strategies to address MDR and biofilm-associated infections.