Summary information and primary citation
- PDB-id
- 4bul; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- isomerase
- Method
- X-ray (2.6 Å)
- Summary
- Novel hydroxyl tricyclics (e.g. gsk966587) as potent inhibitors of bacterial type iia topoisomerases
- Reference
- Miles TJ, Hennessy AJ, Bax B, Brooks G, Brown BS, Brown P, Cailleau N, Chen D, Dabbs S, Davies DT, Esken JM, Giordano I, Hoover JL, Huang J, Jones GE, Kusalakumari Sukmar SK, Spitzfaden C, Markwell RE, Minthorn EA, Rittenhouse S, Gwynn MN, Pearson ND (2013): "Novel Hydroxyl Tricyclics (E.G., Gsk966587) as Potent Inhibitors of Bacterial Type Iia Topoisomerases." Bioorg.Med.Chem.Lett., 23, 5437. doi: 10.1016/J.BMCL.2013.07.013.
- Abstract
- During the course of our research to find novel mode of action antibacterials, we discovered a series of hydroxyl tricyclic compounds that showed good potency against Gram-positive and Gram-negative pathogens. These compounds inhibit bacterial type IIA topoisomerases. Herein we will discuss structure-activity relationships in this series and report advanced studies on compound 1 (GSK966587) which demonstrates good PK and in vivo efficacy properties. X-ray crystallographic studies were used to provide insight into the structural basis for the difference in antibacterial potency between enantiomers.
