Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 23, Issue 7, Pages 2035-2043Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2013.02.019
Keywords
TgENR; Triclosan; ADMET; Toxoplasma
Categories
Funding
- NIAID [U01 AI082180-0101]
- Wellcome Trust
- Mann and Cornwell family
- Rooney-Alden family
- Taub family
- Engel family
- Mussilami family
- MRC [G1000567]
- Medical Research Council [G1000567] Funding Source: researchfish
- MRC [G1000567] Funding Source: UKRI
Ask authors/readers for more resources
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. (C) 2013 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available