Interaction of heterocyclic compounds with efflux pumps in Salmonella Enterica

Abstract

Antibiotics are powerful medicines that fight diseases caused by bacterial infections. They either kill bacteria or keep them from reproducing. But there is another side of such treatment using antibiotics – too frequent usage of it for human and farm, water animal therapy for the growth control. Such 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. Heterocyclic compounds such as 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. Such compounds bearing amino alkyl side chain connected to the nitrogen atom are important in medicinal chemistry. The investigation of substituted 10H-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. 9H-Carbazole and its derivatives are an important type of nitrogen-containing aromatic heterocyclic compounds, it possess desirable electronic and charge-transport properties, large π-conjugated system. The various functional groups could be easily introduced into the structurally rigid carbazolyl ring. [...]