N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors

Summary, in English

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: Ingela Fritzson; Paul T. P. Bedingfield; Anders Sundin; Glenn McConkey; Ulf Nilsson
• Department/s: Centre for Analysis and Synthesis
• Publishing year: 2011
• Language: English
• Pages: 895-898
• Publication/Series: MedChemComm
• Volume: 2
• Issue: 9
• Links: http://dx.doi.org/10.1039/c1md00118c
• Document type: Journal article
• Publisher: Royal Society of Chemistry
• Topic: Medicinal Chemistry
• Status: Published
• ISBN/ISSN/Other: ISSN: 2040-2511