S35: Plant natural products as bacterial biofilm inhibitors

Sequoia’s internal antibacterial program based on screening of our natural product library has discovered a variety of novel compounds that show great promise in the inhibition of bacterial biofilm growth.  Current synthetic efforts have shown them to be synthetically accessible and are amenable to chemical modification in order to increase their potency.  Our research to date indicates that these compounds that we have identified as biofilm inhibitors appear to prevent the formation or maintenance of a protective coating produced by bacteria that increase the bacteria’s resistance to immune responses and antibiotics and enable their attachment to surfaces including human cells, medical devices and teeth.  Our lead compounds have demonstrated broad-spectrum inhibition against Streptococci spp., Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa.  A review of our natural product discovery process using examples of working with microgram quantities of material to perform isolation and structure elucidation as well as examples of biological screening of our lead compounds will be presented.