2. Academic Validation
  3. Design, synthesis, and biological activity of diaryl ether inhibitors of Toxoplasma gondii enoyl reductase

Design, synthesis, and biological activity of diaryl ether inhibitors of Toxoplasma gondii enoyl reductase

  • Bioorg Med Chem Lett. 2013 Apr 1;23(7):2035-43. doi: 10.1016/j.bmcl.2013.02.019.
Gang Cheng 1,  Stephen P Muench,  Ying Zhou,  Gustavo A Afanador,  Ernest J Mui,  Alina Fomovska,  Bo Shiun Lai,  Sean T Prigge,  Stuart Woods,  Craig W Roberts,  Mark R Hickman,  Patty J Lee,  Susan E Leed,  Jennifer M Auschwitz,  David W Rice,  Rima McLeod
Affiliations

Affiliation

  • 1 Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA.
PMID: 23453069 DOI: 10.1016/j.bmcl.2013.02.019
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.

Figures
Products