Design and Synthesis of a Triazole‐based Small Molecule Library for the Inhibition of Bacterial Quorum Sensing

Abstract

With the rise of antibiotic resistance, finding novel methods of targeting bacteria and treating disease is in high demand. One target system of interest is the bacterial quorum sensing system. This process involves bacteria communicating using small signaling molecules. This communication allows bacteria to engage in group behaviors such as biofilm formation and release of infective agents. It has been demonstrated that synthetic small molecules can be used to inhibit such behaviors. Although some success has been had, the design of more diverse libraries could lead to more efficient modulators, easier synthetic routes, and increased understanding of the quorum sensing pathway. The research presented here focuses on the design and synthesis of a library of adamantyl‐derived triazoles. The triazole scaffold was chosen because of its ease of synthesis, and a wide selection of terminal and di‐substituted alkynes were chosen based on similarities to natural quorum sensing molecules. Some functionalities include, a five membered ring with heteroatoms and carbon chains of varying lengths. Upon synthesis and purification, these molecules are assayed for their ability to inhibit quorum sensing in Vibrio fischeri. Vibrio fischeri is used because its quorum sensing system is similar to other Gram‐negative bacteria that are known to cause human infections (i.e. Pseudomonas aeruginosa), but it is non‐pathogenic. Additionally, this species' bioluminescence is controlled by a quorum‐dependent pathway, which allows for easy detection of quorum sensing inhibition via quantification of light production. To date, the molecules that have been tested have not been found to inhibit bacterial quorum sensing, however, the library continues to grow with different functionalities. Herein, we will describe the design and synthesis of a growing triazole‐based library as well as data regarding the ability of these molecules to inhibit quorum sensing in Vibrio fischeri.Support or Funding InformationCEK received partial funding from the Pennsylvania Academy of Sciences.Mercyhurst University provided the remaining funding.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.