Design and synthesis of indolo[2,3-a]quinolizin-7-one inhibitors of the ZipA-FtsZ interaction.
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Jennings LD, Foreman KW, Rush TS 3rd, Tsao DH, Mosyak L, Li Y, Sukhdeo MN, Ding W, Dushin EG, Kenny CH, Moghazeh SL, Petersen PJ, Ruzin AV, Tuckman M, Sutherland AG
Design and synthesis of indolo[2,3-a]quinolizin-7-one inhibitors of the ZipA-FtsZ interaction.
Bioorg Med Chem Lett. 2004 Mar 22;14(6):1427-31.
- PubMed ID
- 15006376 [ View in PubMed]
- Abstract
The binding of FtsZ to ZipA is a potential target for antibacterial therapy. Based on a small molecule inhibitor of the ZipA-FtsZ interaction, a parallel synthesis of small molecules was initiated which targeted a key region of ZipA involved in FtsZ binding. The X-ray crystal structure of one of these molecules complexed with ZipA was solved. The structure revealed an unexpected binding mode, facilitated by desolvation of a loosely bound surface water.