1059628-87-3Relevant articles and documents
On the mechanism of berberine-INF55 (5-Nitro-2-phenylindole) hybrid antibacterials
Dolla, Naveen K.,Chen, Chao,Larkins-Ford, Jonah,Rajamuthiah, Rajmohan,Jagadeesan, Sakthimala,Conery, Annie L.,Ausubel, Frederick M.,Mylonakis, Eleftherios,Bremner, John B.,Lewis, Kim,Kelso, Michael J.
, p. 1471 - 1480 (2014)
Berberine-INF55 hybrids are a promising class of antibacterials that combine berberine and the NorA multidrug resistance pump inhibitor INF55 (5-nitro-2-phenylindole) together in one molecule via a chemically stable linkage. Previous studies demonstrated the potential of these compounds for countering efflux-mediated antibacterial drug resistance but they didn't establish whether the compounds function as originally intended, i.e. with the berberine moiety providing antibacterial activity and the attached INF55 component independently blocking multidrug resistance pumps, thereby enhancing the activity of berberine by reducing its efflux. We hypothesised that if the proposed mechanism is correct, then hybrids carrying more potent INF55 pump inhibitor structures should show enhanced antibacterial effects relative to those bearing weaker inhibitors. Two INF55 analogues showing graded reductions in NorA inhibitory activity compared with INF55 were identified and their corresponding berberine-INF55 hybrids carrying equivalent INF55 inhibitor structures synthesised. Multiple assays comparing the antibacterial effects of the hybrids and their corresponding berberine-INF55 analogue combinations showed that the three hybrids all show very similar activities, leading us to conclude that the antibacterial mechanism(s) of berberine-INF55 hybrids is different from berberine-INF55 combinations.
Synthesis of berberineefflux pump inhibitor hybrid antibacterials
Bremner, John B.,Kelso, Michael J.
experimental part, p. 3561 - 3568 (2011/03/17)
This article describes the compact synthesis of two isomeric dual-action hybrid antimicrobials where the 13-position of the antibacterial berberine has been linked via 3′-and 4′-methylene bridges to INF55 (5-nitro-2-phenylindole), an inhibitor of the bacterial NorA multidrug-resistance pump. Copyright Taylor & Francis Group, LLC.
Structure-activity relationships of 2-aryl-1H-indole inhibitors of the NorA efflux pump in Staphylococcus aureus
Ambrus, Joseph I.,Kelso, Michael J.,Bremner, John B.,Ball, Anthony R.,Casadei, Gabriele,Lewis, Kim
scheme or table, p. 4294 - 4297 (2009/04/06)
The synthesis of 22 2-aryl-1H-indoles, including 12 new compounds, has been achieved via Pd- or Rh-mediated methodologies, or selective electrophilic substitution. All three methods were based on elaborations from simple indole precursors. SAR studies on
