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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


Brokamp, Renate; Bergmann, Bärbel; Müller, Ingrid B; Bienz, Stefan (2014). 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. Bioorganic & Medicinal Chemistry, 22(6):1832-1837.

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 IC$_{50}$ 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.

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 IC$_{50}$ 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:8 February 2014
Deposited On:12 Feb 2015 13:02
Last Modified:21 Nov 2017 17:44
Publisher:Elsevier
ISSN:0968-0896
Publisher DOI:https://doi.org/10.1016/j.bmc.2014.01.057

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