Design And Synthesis Of 15-Membered Macrolide Efflux Pump Inhibitors Against Multidrug Resistant Bacteria

With the widespread clinical use of antibiotics, there is a great decrease in the morbidity and mortality of infected people. However, the emergence of bacterial resistance as responding to the antibiotics directly leads to reducing the curative effect, even no effect. Therefore, it is an urgent problem to be resolve in the world to find new antibiotics against resistant bacteria.The existence of efflux pumps in bacteria is one of the most reasons for the bacterial resistance to antibiotics. The overexpression of efflux pumps can increase the efflux of drugs from bacterial bodies, cut down drug concentration in bacterial bodies and result in a decrease in curative effect. Furthermore, the synergistic effect of efflux pumps with other resistant mechanisms together contributes to high bacterial resistance which is very difficult for antibiotics to overcome. Fortunately, efflux pump inhibitors can not only inhibit the efflux effect of the pumps, but also recover the sensitivity of antibiotics to bacteria and increase the therapeutic effect of antibiotics. In addition, they are also widely used in improving the pharmacokinetic properties of some drugs, including enhancing oral bioavailability, degrading the clearance of liver or kidney, etc.According to the homology of amino acid sequence, efflux pumps are divided into five big families in which Resistance Nodulation cell Division family (RND) is the main efflux pump family only existed in Gram-negative bacteria and results in the...