Novel cinnamic acid-based PET derivatives as quorum sensing modulators

Abstract

Poly(ethylene terephthalate) (PET) is widely used material in the healthcare due to its mechanical properties including resistance to chemicals and abrasion. However, it is susceptible to bacterial attachment and contamination. This study addresses some newly designed model compounds of PET with antimicrobial properties that could potentially be incorporated into PET materials. All compounds were synthesized for the first time by labeling an integral part of PET with chromophores in the form of esters of cinnamic and ferulic acids. After complete structural characterization, the effect of new compounds on microbial growth and communication (quorum sensing, QS) was analyzed and further investigated using molecular docking. The obtained results indicate that the introduction of chromophores that have one part of cinnamic acid enriched with a methoxy functional group in them acts as QS modulators. Moreover, compounds exhibited dose-dependent selectivity toward QS signaling pathways and the highest tested concentration of compounds showed Pseudomonas Quinolone Signal (PQS) inhibitory activity suggesting that these compounds have a potential effect on pyocyanin production. Docking studies demonstrated that compounds hold binding power to all four QS protein targets (LuxP, periplasmatic protein that binds AI-2 inducer and forms a complex able to transduce the autoinducer signal, RhIR protein that is a key QS transcriptional regulator that activates the genes involved in the synthesis of rhamnolipids and pyocyanin, AbaI protein that has a role in QS signal transduction, and LasR protein which is a key QS transcriptional regulator that activates transcription of genes coding for some virulence-associated traits) while the highest binding strength is observed with compounds 2 and 6 containing single cinnamic acid fragment, suggesting their further biomedical application.