Interaction of Phenothiazine and Carbazole-based compounds with efflux pumps in Salmonella Enterica

Abstract

Antibiotics are powerful medicines that fight diseases caused by bacterial infections. Used properly, antibiotics save lives: they either kill bacteria or keep them from reproducing. But there is another side of it therapy using antibiotics - overusing or too frequent usage for human, as well as for farm animal therapy. Such unconsidered usage of antibiotics resulted in resistance of pathogenic bacteria to multiple drugs because many of commonly used antibiotics are substrates of efflux pumps. Inhibitors of efflux pumps have a great potential as pharmacological agents that restore the drug susceptibility of multidrug resistant pathogens. It is very important to discover compounds inhibiting the efflux pumps and enhancing the efficiency of antibiotics as well as to investigate the mechanisms of efflux pumps modulation. Derivatives of carbazole and phenothiazine could be considered as potential efflux pump inhibitors and substrates. Phenothiazine is heterocyclic compound with two benzene rings linked in a tricyclic system through nitrogen and sulfur atoms. For many years phenoathiazine has been used in veterinary medicine as an antihelminic drug. These compounds having amino alkyl side chain connected to the nitrogen atom are playing crucial. role in medicinal chemistry. The investigation of substituted lOH-phenothiazines has strong growth during the last years because of a wide range of applications. Such derivatives are widely employed as antibacterial, antiviral, anti-inflammatory, anticancer, sedatives or tranquilizers agents. The slight change in the structure of these compounds causes distinguishable difference in their biological activities. Carbazole is also heterocyclic compound with two benzene rings linked in a tricyclic system through nitrogen atom and also could be employed as biological active compound. [...]