Diverted total synthesis of falcitidin acyl tetrapeptides as new antimalarial leads

Santosh R. Kotturi, Brinda Somanadhan, Jun Hong Ch'Ng, Kevin S.W. Tan, Mark S. Butler, Martin J. Lear

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 languageEnglish
Pages (from-to)1949-1951
Number of pages3
JournalTetrahedron Letters
Volume55
Issue number11
DOIs
Publication statusPublished - 2014 Mar 12

Keywords

  • Antimalarial agents
  • Falcitidin
  • Natural products
  • Tetrapeptide
  • Trifluoromethyl

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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    Kotturi, S. R., Somanadhan, B., Ch'Ng, J. H., Tan, K. S. W., Butler, M. S., & Lear, M. J. (2014). Diverted total synthesis of falcitidin acyl tetrapeptides as new antimalarial leads. Tetrahedron Letters, 55(11), 1949-1951. https://doi.org/10.1016/j.tetlet.2014.02.008