Diverted total synthesis of falcitidin acyl tetrapeptides as new antimalarial leads

Kotturi, Santosh R. and Somanadhan, Brinda and Ch’ng, Jun-Hong and Tan, Kevin S.-W. and Butler, Mark S. and Lear, Martin J. (2014) Diverted total synthesis of falcitidin acyl tetrapeptides as new antimalarial leads. Tetrahedron Letters, 55 (11). pp. 1949-1951. ISSN 0040-4039

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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.

Keywords:Falcitidin, Tetrapeptide, Trifluormethyl, Natural products, Anitmalarial agents, JCNotOpen
Subjects:F Physical Sciences > F160 Organic Chemistry
F Physical Sciences > F150 Medicinal Chemistry
Divisions:College of Science > School of Chemistry
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ID Code:17098
Deposited On:16 Apr 2015 12:14

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