Synthesis and evaluation of the efficiency of RND-type efflux pump inhibitors

Abstract

Salmonella enterica serovar Typhimurium is the main cause of food poisoning and is the second most common cause of bacterial diarrhea [1-2]. Resistance-nodulation-cell division (RND)-type multidrug resistance efflux pumps are the main reason of Salmonella enterica cell resistance to antibiotics. It is important to investigate the mechanism of efflux pump inhibition. A membrane voltage indicator tetraphenylphosphonium (TPP+) in combination with the efflux pump inhibitor can be used to monitor the activity of RND-type efflux pumps in bacteria. The aim of our work was to synthesize small dipeptide inhibitors and to evaluate the efficiency of RND-type efflux pump inhibition in S. enterica cells. We studied effects of the synthesized RND-type efflux pump inhibitors on accumulation of TPP⁺ ions in S. enterica. In this work we present synthesis of target inhibitors - phenylalanyl-arginyl-β-naphthylamide, phenylalanyl-lysinyl--naphthylamide and data of the electrochemical assay of an indicator compound accumulation of efflux pumps in bacteria. Synthesis steps also data of the effective concentrations of the inhibitors and the efficiency of inhibition of RND-type efflux pump activity will be presented.