Pharmacological activities, SARs and targets of heterocyclic derivatives as QSIs against bacteria multidrug resistance.

The escalating global crisis of bacterial multidrug resistance (MDR), particularly the recalcitrant infections caused by Pseudomonas aeruginosa, underscores an urgent need for novel therapeutic strategies. In contrast to conventional bactericidal antibiotics, antivirulence approaches targeting the quorum sensing (QS) system offer a promising paradigm by attenuating pathogenicity without exerting lethal selective pressure, thereby potentially mitigating resistance development. This review provides a comprehensive and systematic analysis of the research progress on heterocyclic derivatives as QS inhibitors reported between 2020 and 2025. It is specifically focused on two principal structural classes: nitrogen-containing heterocycles (e.g., quinolines, (inhibition rate: 40.3%-87.4%), quinazolines (IC50 = 0.3-6.9 μM), pyridines (IC50 = 0.3-6.6 μM), indoles (IC50 = 0.2-0.3 μM), thiazoles (IC50 = 0.4-131.5 μM)) and oxygen-containing heterocycles (e.g., furans (inhibition rate: 53.0%-86.8%), flavonoids (inhibition rate: 32.0%-90.9%), coumarins (inhibition rate: 50.0%-73.0%)). For these compounds, biological activities, structure-activity relationships, and targets are critically discussed. This work aims to consolidate recent advances and offer valuable insights for the rational design and development of next-generation anti-infective agents targeting bacterial communication pathways.