title: Design, synthesis, and biological activity of diaryl ether inhibitors of Toxoplasma gondii enoyl reductase.
abstract: Triclosan is a potent inhibitor of Toxoplasma gondii enoyl reductase (TgENR), which is an essential enzyme for parasite survival. In view of triclosan's poor druggability, which limits its therapeutic use, a new set of B-ring modified analogs were designed to optimize its physico-chemical properties. These derivatives were synthesized and evaluated by in vitro assay and TgENR enzyme assay. Some analogs display improved solubility, permeability and a comparable MIC50 value to that of triclosan. Modeling of these inhibitors revealed the same overall binding mode with the enzyme as triclosan, but the B-ring modifications have additional interactions with the strongly conserved Asn130.
authors: Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA.
authors: Gang
authors: G
authors: Cheng
authors: Stephen P
authors: SP
authors: Muench
authors: Ying
authors: Y
authors: Zhou
authors: Gustavo A
authors: GA
authors: Afanador
authors: Ernest J
authors: EJ
authors: Mui
authors: Alina
authors: A
authors: Fomovska
authors: Bo Shiun
authors: BS
authors: Lai
authors: Sean T
authors: ST
authors: Prigge
authors: Stuart
authors: S
authors: Woods
authors: Craig W
authors: CW
authors: Roberts
authors: Mark R
authors: MR
authors: Hickman
authors: Patty J
authors: PJ
authors: Lee
authors: Susan E
authors: SE
authors: Leed
authors: Jennifer M
authors: JM
authors: Auschwitz
authors: David W
authors: DW
authors: Rice
authors: Rima
authors: R
authors: McLeod
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014122:Toxoplasma / Q000201:enzymology*; D014260:Triclosan / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D014260:Triclosan; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)