Projects per year
Abstract
The bifunctional enzyme N5,N10-methylenetetrahydrofolate dehydrogenase/cyclo hydrolase (FolD) is essential for growth in Trypanosomatidae. We sought to develop inhibitors of Trypanosoma brucei FolD (TbFolD) as potential antiparasitic agents. Compound 2 was synthesized, and the molecular structure was unequivocally assigned through X-ray crystallography of the intermediate compound 3. Compound 2 showed an IC50 of 2.2 μM, against TbFolD and displayed antiparasitic activity against T. brucei (IC50 49 μM). Using compound 2, we were able to obtain the first X-ray structure of TbFolD in the presence of NADP+ and the inhibitor, which then guided the rational design of a new series of potent TbFolD inhibitors.
Original language | English |
---|---|
Pages (from-to) | 7938-7948 |
Number of pages | 11 |
Journal | Journal of Medicinal Chemistry |
Volume | 58 |
Issue number | 20 |
Early online date | 31 Aug 2015 |
DOIs | |
Publication status | Published - 22 Oct 2015 |
Fingerprint
Dive into the research topics of 'Characterization of 2,4-Diamino-6-oxo-1,6-dihydropyrimidin-5-yl Ureido based inhibitors of Trypanosoma brucei FolD and testing for antiparasitic activity'. Together they form a unique fingerprint.Projects
- 2 Finished
-
State-of-the-Art Facilities for Structural Biology at the University of Dundee
Hunter, B., Lilley, D., Owen-Hughes, T., Wyatt, P. & van Aalten, D.
1/03/12 → 28/02/17
Project: Research
Profiles
-
Hunter, Bill
- Biological Chemistry and Drug Discovery - Professor & Structural Biology
Person: Academic