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N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors

Fritzson, Ingela LU ; Bedingfield, Paul T. P.; Sundin, Anders LU ; McConkey, Glenn and Nilsson, Ulf LU (2011) In MedChemComm 2(9). p.895-898
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.
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
MedChemComm
volume
2
issue
9
pages
895 - 898
publisher
Royal Society of Chemistry
external identifiers
  • wos:000295710300012
  • scopus:80052363272
ISSN
2040-2511
DOI
10.1039/c1md00118c
language
English
LU publication?
yes
id
dea89224-b79b-4e71-8f5d-3ac1cca0d179 (old id 2212662)
date added to LUP
2011-11-23 13:58:13
date last changed
2017-08-06 03:04:43
@article{dea89224-b79b-4e71-8f5d-3ac1cca0d179,
  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.},
  author       = {Fritzson, Ingela and Bedingfield, Paul T. P. and Sundin, Anders and McConkey, Glenn and Nilsson, Ulf},
  issn         = {2040-2511},
  language     = {eng},
  number       = {9},
  pages        = {895--898},
  publisher    = {Royal Society of Chemistry},
  series       = {MedChemComm},
  title        = {N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors},
  url          = {http://dx.doi.org/10.1039/c1md00118c},
  volume       = {2},
  year         = {2011},
}