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Bioorg Med Chem. 2014 Mar 15;22(6):1832-7. doi: 10.1016/j.bmc.2014.01.057. Epub 2014 Feb 8.

Stereoselective preparation of pyridoxal 1,2,3,4-tetrahydro-β-carboline derivatives and the influence of their absolute and relative configuration on the proliferation of the malaria parasite Plasmodium falciparum.

Author information

  • 1Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
  • 2Biochemical Parasitology, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, D-20359 Hamburg, Germany.
  • 3Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Electronic address: stefan.bienz@chem.uzh.ch.

Abstract

We have selectively synthesized by Pictet-Spengler condensation of tryptophan and pyridoxal the four stereoisomers of a pyridoxal β-carboline derivative that was designed to inhibit the proliferation of Plasmodium falciparum. Biological investigation of the four compounds revealed that they all inhibit the growth of P. falciparum. With an IC50 value of 8 ± 1 μM, the highest inhibitory effect on the proliferation of the parasite was found for the 1,3-trans-substituted tetrahydro-β-carboline that was obtained from d-tryptophan. Lower activity was found for its enantiomer, while the two diastereomeric cis-products were markedly less effective. Apparently a distinct spacial orientation of the carboxyl group of the substituted tetrahydropyridine unit of the compounds is needed for high activity, while the absolute configuration of the molecules is of lesser importance.

Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

Malaria; PLP dependent enzyme; Plasmodium falciparum; Pyridoxal; Tetrahydro-β-carboline

PMID:
24565970
[PubMed - indexed for MEDLINE]
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