N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Ingela Fritzson
  • Paul T. P. Bedingfield
  • Anders Sundin
  • Glenn McConkey
  • Ulf Nilsson
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Läkemedelskemi
Originalspråkengelska
Sidor (från-till)895-898
TidskriftMedChemComm
Volym2
Utgivningsnummer9
StatusPublished - 2011
PublikationskategoriForskning
Peer review utfördJa