Diverted total synthesis of falcitidin acyl tetrapeptides as new antimalarial leads

Kotturi, Santosh R., Somanadhan, Brinda, Ch'Ng, Jun-Hong, Tan, Kevin S.-W., Butler, Mark S. and Lear, Martin J. (2014) Diverted total synthesis of falcitidin acyl tetrapeptides as new antimalarial leads. Tetrahedron Letters, 55 11: 1949-1951. doi:10.1016/j.tetlet.2014.02.008


Author Kotturi, Santosh R.
Somanadhan, Brinda
Ch'Ng, Jun-Hong
Tan, Kevin S.-W.
Butler, Mark S.
Lear, Martin J.
Title Diverted total synthesis of falcitidin acyl tetrapeptides as new antimalarial leads
Journal name Tetrahedron Letters   Check publisher's open access policy
ISSN 0040-4039
1873-3581
Publication date 2014-03-12
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.tetlet.2014.02.008
Open Access Status
Volume 55
Issue 11
Start page 1949
End page 1951
Total pages 3
Place of publication Oxford, United Kingdom
Publisher Pergamon Press
Language eng
Subject 1303 Biochemistry
3002 Drug Discovery
1605 Organic Chemistry
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. (c) 2014 Elsevier Ltd. All rights reserved.
Formatted 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.
Keyword Falcitidin
Tetrapeptide
Trifluoromethyl
Natural products
Antimalarial agents
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID T20681112
NMRC/1310/2011
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Official Audit
Institute for Molecular Bioscience - Publications
 
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