AI Article Synopsis
- Researchers are targeting the enzyme FolD in Trypanosoma brucei, a parasite crucial for its growth, to develop new antiparasitic treatments.
- They synthesized a compound (Compound 2) with a specific structure confirmed by X-ray crystallography, which showed effectiveness against the enzyme and the parasite.
- The study led to the first X-ray structure of TbFolD with the inhibitor and NADP(+), paving the way for designing more effective TbFolD inhibitors.
Article Abstract
The bifunctional enzyme N(5),N(10)-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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621507 | PMC |
| http://dx.doi.org/10.1021/acs.jmedchem.5b00687 | DOI Listing |
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