Modification of Triclosan Scaffold in Search of Improved Inhibitors for Enoyl-Acyl Carrier Protein (ACP) Reductase in Toxoplasma gondii (pages 1138–1160)
Dr. Jozef Stec, Alina Fomovska, Gustavo A. Afanador, Prof. Dr. Stephen P. Muench, Dr. Ying Zhou, Bo-Shiun Lai, Prof. Dr. Kamal El Bissati, Dr. Mark R. Hickman, Patty J. Lee, Susan E. Leed, Jennifer M. Auschwitz, Dr. Caroline Sommervile, Dr. Stuart Woods, Prof. Dr. Craig W. Roberts, Prof. Dr. David Rice, Dr. Sean T. Prigge, Dr. Rima McLeod and Prof. Dr. Alan P. Kozikowski
Version of Record online: 14 JUN 2013 | DOI: 10.1002/cmdc.201300050
Crystal structures of the TgENR–NAD+–triclosan complex (A) with docked compounds 16 c (B) and 37 c (C): The latter two compounds have high potency, improved physicochemical properties, and lower toxicity than triclosan. Two new hydrogen bonding interactions with the surrounding TgENR residues are likely to be decisive for the high inhibitory activity of 16 c. Compound 37 c is bulkier, but binds in the same manner as triclosan.