Journal of Medicinal Chemistry p. 867 - 891 (2016)
Update date:2022-08-15
Topics:
Lepri, Susan
Buonerba, Federica
Goracci, Laura
Velilla, Irene
Ruzziconi, Renzo
Schindler, Bryan D.
Seo, Susan M.
Kaatz, Glenn W.
Cruciani, Gabriele
Antibiotic resistance represents a worldwide concern, especially regarding the outbreak of methicillin-resistant Staphylococcus aureus, a common cause for serious skin and soft tissues infections. A major contributor to Staphylococcus aureus antibiotic resistance is the NorA efflux pump, which is able to extrude selected antibacterial drugs and biocides from the membrane, lowering their effective concentrations. Thus, the inhibition of NorA represents a promising and challenging strategy that would allow recycling of substrate antimicrobial agents. Among NorA inhibitors, the indole scaffold proved particularly effective and suitable for further optimization. In this study, some unexplored modifications on the indole scaffold are proposed. In particular, for the first time, substitutions at the C5 and N1 positions have been designed to give 48 compounds, which were synthesized and tested against norA-overexpressing S. aureus. Among them, 4 compounds have NorA IC50 values lower than 5.0 μM proving to be good efflux pump inhibitor (EPI) candidates. In addition, preliminary data on their ADME (absorption, distribution, metabolism, and excretion) profile is reported.
View Morezhejiang huangyan wanfeng pharm chem co.ltd
Contact:+86-576- 84160728
Address:No. 5 Dazha Road, Economic,Development Zone(JiangKou), Zhejiang, China
Shanghai shibo Chemical Co., Ltd
Contact:+86-021-60753516
Address:688 Qiushi Road, Jinshan High-tech Park, Shanghai, China,201512
Changzhou Jiana Chemical Co.,Ltd
website:http://www.jianachem.com
Contact:86-0519-88731808
Address:Zhenglu Town Wujin City, Jiangsu Province
Nanjing Legend Pharmaceutical & Chemical Co., Ltd.
Contact:+86-25-83767696
Address:14-7 Zhongshan Lu Guluo District, Nanjing
Hunan Shineway Enterprise Co., Ltd.
Contact:+86-731-86303875
Address:118, Huanghua International Airport Road, Huanghua Town, Changsha, Hunan 410137, China
Doi:10.1016/S0022-1139(03)00145-3
(2003)Doi:10.1039/a807003b
(1999)Doi:10.1016/j.jfluchem.2008.04.004
(2008)Doi:10.1016/S0040-4020(98)01155-7
(1999)Doi:10.1039/j39710001694
(1971)Doi:10.1016/S0040-4020(98)01087-4
(1999)