The effect of Coumaperine, Piperlongumine, Pterostilbene and Curcumin derivatives on Quorum Sensing Inhibition, Anti-Bacterial and Anti-Inflammatory Activities

In this work we searched for natural-based plant compounds as a strategy for finding new antibiotics, elimination/prevention of resistant biofilm-forming bacteria and inhibition of inflammation. We tested 55 derivatives of the following natural compounds: Coumaperine, Piprelongumine, Pterostilbene and Curcumin. Biofilms clinging to damp surfaces are highly organized microbial structures that increase bacterial survival and antibiotic resistance. The formation of biofilms on medical devices such as implants and catheters often induce inflammation, rejection and infection. Bacterial quorum sensing signals induce the formation of biofilms. Quorum sensing (QS) inhibition assays were performed using the bio-reporter bacteria Chromobacterium violaceum and Agrobacterium tumefaciens. Antibacterial activity tests were carried out on Gram positive and Gram negative bacteria. Inflammation is a reaction of the immune system to injury, infection and foreign bodies. Since implants/catheters often induce inflammation, we tested the effects of these compounds in reducing inflammation by NF-κB inhibition. NF-κB is a pro-inflammatory transcription factor in mammalian cells. NF-κB inhibition was determined in a NF-κB-luciferase reporter gene assay in Hodgkin`s lymphoma cells line L428 with constitutive NF-κB activation. Our results show that some of these compounds have activity in more than one test. For example, CP-286 and PL-18 have low cellular toxicity, inhibit NF-κB and QS but are not active as antibiotic. CP-287 has antibacterial activity and inhibit QS but is not anti-inflammatory. Other compounds and their properties will be also presented. The development of new effective molecules may become a much-needed additional arsenal to fight morbidity and mortality due to infection and inflammation.