Antibacterial activity of berberine-NorA pump inhibitor hybrids with a methylene ether linking group

作者:Samosorn Siritron*; Tanwirat Bongkot; Muhamad Nussara; Casadei Gabriele; Tomkiewicz Danuta; Lewis Kim; Suksamrarn Apichart; Prammananan Therdsak; Gornall Karina C; Beck Jennifer L; Bremner John B
来源:Bioorganic & Medicinal Chemistry, 2009, 17(11): 3866-3872.
DOI:10.1016/j.bmc.2009.04.028

摘要

Conjugation of the NorA substrate berberine and the NorA inhibitor 5-nitro-2-phenyl-1H-indole via a methylene ether linking group gave the 13-substituted berberine-NorA inhibitor hybrid, 3. A series of simpler arylmethyl ether hybrid structures were also synthesized. The hybrid 3 showed excellent antibacterial activity (MIC Staphylococcus aureus, 1.7 mu M), which was over 382-fold more active than the parent antibacterial berberine, against this bacterium. This compound was also shown to block the NorA efflux pump in S. aureus.