2. Academic Validation
  3. Novel 2-Phenoxyanilide Congeners Derived from a Hit Structure of the TCAMS: Synthesis and Evaluation of Their in Vitro Activity against Plasmodium falciparum

Novel 2-Phenoxyanilide Congeners Derived from a Hit Structure of the TCAMS: Synthesis and Evaluation of Their in Vitro Activity against Plasmodium falciparum

  • Molecules. 2016 Feb 17;21(2):223. doi: 10.3390/molecules21020223.
Thomas Weidner 1,  Abed Nasereddin 2,  Lutz Preu 3,  Johann Grünefeld 4,  Ron Dzikowski 5,  Conrad Kunick 6 7
Affiliations

Affiliations

  • 1 Institut für Medizinische und Pharmazeutische Chemie, Technische Universität Braunschweig, Beethovenstraße 55, 38106 Braunschweig, Germany. t.weidner@tu-braunschweig.de.
  • 2 Department of Microbiology and Molecular Genetics, IMRIC, The Kuvin Center for the Study of Infectious and Tropical Diseases, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. abedn@ekmd.huji.ac.il.
  • 3 Institut für Medizinische und Pharmazeutische Chemie, Technische Universität Braunschweig, Beethovenstraße 55, 38106 Braunschweig, Germany. l.preu@tu-braunschweig.de.
  • 4 Institut für Medizinische und Pharmazeutische Chemie, Technische Universität Braunschweig, Beethovenstraße 55, 38106 Braunschweig, Germany. j.gruenefeld@tu-braunschweig.de.
  • 5 Department of Microbiology and Molecular Genetics, IMRIC, The Kuvin Center for the Study of Infectious and Tropical Diseases, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. rond@ekmd.huji.ac.il.
  • 6 Institut für Medizinische und Pharmazeutische Chemie, Technische Universität Braunschweig, Beethovenstraße 55, 38106 Braunschweig, Germany. c.kunick@tu-braunschweig.de.
  • 7 Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35A, 38106 Braunschweig, Germany. c.kunick@tu-braunschweig.de.
PMID: 26901174 DOI: 10.3390/molecules21020223
Abstract

The Tres Cantos Antimalarial Compound Set (TCAMS) is a publicly available compound library which contains 13533 hit structures with confirmed activity against Plasmodium falciparum, the infective agent responsible for malaria tropica. The TCAMS provides a variety of starting points for the investigation of new antiplasmodial drug leads. One of the promising compounds is TCMDC-137332, which seemed to be a good starting point due to its antiplasmodial potency and its predicted physicochemical properties. Several new analogues based on a 2-phenoxyanilide scaffold were synthesized by standard amide coupling reactions and were fully characterized regarding their identity and purity by spectroscopic and chromatographic methods. Furthermore, the results of the biological evaluation of all congeners against Plasmodium falciparum NF54 strains are presented. The findings of our in vitro screening could not confirm the presumed nanomolar antiplasmodial activity of TCMDC-137332 and its derivatives.

Keywords

2-phenoxyanilide; Malaria; Plasmodium falciparum; TCAMS; TCMDC-137332; diarylether; luciferase.

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