Abstract
We report not only the convergent total synthesis of falcitidin, a natural inhibitor of falcipain-2 from myxobacterium Chitinophaga, but also its diversification into a new antimalarial class of N-acyl tetrapeptides (Acyl-His-Ile-Val-Pro-NH2). Despite the lack of whole-cell activity of falcitidin itself, our study led to the identification of a trifluoromethyl (CF3) analogue displaying sub-micromolar IC50 activity against Plasmodium falciparum 3D7 in a standard blood-cell assay, but only when N-tritylated on its histidine (imidazole) residue.
Original language | English |
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Pages (from-to) | 1949-1951 |
Number of pages | 3 |
Journal | Tetrahedron Letters |
Volume | 55 |
Issue number | 11 |
DOIs | |
Publication status | Published - 2014 Mar 12 |
Externally published | Yes |
Keywords
- Antimalarial agents
- Falcitidin
- Natural products
- Tetrapeptide
- Trifluoromethyl
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry