Multidrug efflux systems play a prominent role in medicine, as they are important\ncontributors to bacterial antibiotic resistance. NorA is an efflux pump transporter from the major\nfacilitator superfamily that expels numerous drug compounds across the inner membrane of\nStaphylococcus aureus (S. aureus). The design of novel inhibitors to combat drug efflux could offer new\nopportunities to avoid the problem of antibiotic resistance. In this study, we performed molecular\nmodeling studies in an effort to discover novel NorA efflux pump inhibitors. A group of over\n673 compounds from the PubChem database with a high (>80%) level of similarity to the chemical\nstructure of capsaicin was used to study the binding affinity of small molecule compounds for the\nNorA efflux pump. Ten potential lead compounds displayed a good druggability profile, with one in\nparticular (CID 44330438) providing new insight into the molecular mechanism of the inhibition of\nmajor facilitator superfamily (MFS) efflux pump transporters. It is our hope that the overall strategy\ndescribed in this study, and the structural information of the potential novel inhibitors thus identified,\nwill stimulate others to pursue the development of better drugs to tackle multidrug resistance in\nS. aureus.
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