Polyacetylenes as antibacterial, antibiofilm, and anti-quorum-sensing agents: Sources, chemistry, bioactivities, and 13C-NMR data

The rise of multidrug-resistant bacteria now poses significant challenges, rendering many conventional medicines ineffective and necessitating the search for new antimicrobial agents. Polyacetylenes, both natural and synthetic, possess diverse biological activities, with their remarkable antibacterial potential being particularly significant. This review offers an in-depth evaluation of the therapeutic roles of polyacetylenes as antibacterial, antibiofilm, and anti-quorum-sensing agents, summarizing the tested compounds, their natural sources, the assays employed, and the bacterial strains investigated. It also provides an overview of their biosynthesis, distribution, and pharmacokinetic properties, along with a comprehensive analysis of their chemical classification and 13C-NMR data. Despite decades of research on polyacetylenes, no previous review has systematically integrated their antibacterial mechanisms, biofilm-inhibitory effects, quorum-sensing disruption, and structure-activity relationships (SAR). Our analysis revealed that antibacterial and antibiofilm activities are highly dependent on chain length, conjugation, and specific functional substituents, with halogenation, carbonyl and cinnamate incorporation, and stereochemical configuration significantly modulating potency beyond the previously assumed requirement for hydroxylation. This work fills that gap by compiling information on about 90 polyacetylenes that were reported between 1947 and January 2025. It draws attention to their dual antibacterial mechanism, involving disruption of membrane and downregulation of key QS-related genes, leading to attenuated virulence, suppressed biofilm formation, and marked decrease in bacterial burden. In conclusion, polyacetylenes represent promising antibacterial, antibiofilm, and anti-quorum-sensing candidates, offering valuable scaffolds for developing new therapies against multidrug-resistant infections.