Issue 9, 2011
From the journal:

MedChemComm

N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenaseinhibitors†

Ingela Fritzson,*ab   Paul T. P. Bedingfield,c   Anders P. Sundin,b   Glenn McConkeyc  and  Ulf J. Nilssonb  

* Corresponding authors

a Active Biotech AB, PO Box 724, Lund, Sweden
E-mail: ingela.fritzson@activebiotech.com.
Tel: +46 46 191233

b Organic Chemistry, Lund University, PO Box 124, Lund, Sweden

c Faculty of Biological Sciences, University of Leeds, Leeds, UK

Abstract

In our continuing program to develop Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors, a series of N-substituted salicylamides were synthesized and their ability to selectively inhibit PfDHODH was examined. The synthetic program was based on 2-hydroxy-N-(2-phenylethyl)benzamide (1) that weakly inhibits both PfDHODH and human DHODH (hDHODH). Structure activity relationships were examined for developing derivatives. Selective PfDHODH inhibitors with improved potency were obtained by introducing a 2,2-diphenylethyl substitution on the salicylamidic nitrogen. Biological activity of the most potent compounds was confirmed on parasite infected cells in vitro.

Graphical abstract: N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors

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Article information

DOI
https://doi.org/10.1039/C1MD00118C
Article type
Concise Article
Submitted
05 May 2011
Accepted
03 Jul 2011
First published
21 Jul 2011

Med. Chem. Commun., 2011,2, 895-898

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N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors

I. Fritzson, P. T. P. Bedingfield, A. P. Sundin, G. McConkey and U. J. Nilsson, Med. Chem. Commun., 2011, 2, 895 DOI: 10.1039/C1MD00118C

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