N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors

Ingela Fritzson; Paul T. P. Bedingfield; Anders Sundin; Glenn McConkey; Ulf Nilsson

doi:10.1039/c1md00118c

N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors

Ingela Fritzson, Paul T. P. Bedingfield, Anders Sundin, Glenn McConkey, Ulf Nilsson

Centre for Analysis and Synthesis

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	895-898
Journal	MedChemComm
Volume	2
Issue number	9
DOIs	https://doi.org/10.1039/c1md00118c
Publication status	Published - 2011

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)

Subject classification (UKÄ)

Medicinal Chemistry

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10.1039/c1md00118c

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title = "N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors",

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 = "Ingela Fritzson and Bedingfield, {Paul T. P.} and Anders Sundin and Glenn McConkey and Ulf Nilsson",

note = "The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)",

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doi = "10.1039/c1md00118c",

language = "English",

volume = "2",

pages = "895--898",

journal = "MedChemComm",

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T1 - N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors

AU - Fritzson, Ingela

AU - Bedingfield, Paul T. P.

AU - Sundin, Anders

AU - McConkey, Glenn

AU - Nilsson, Ulf

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1039/c1md00118c

DO - 10.1039/c1md00118c

M3 - Article

SN - 2040-2511

VL - 2

SP - 895

EP - 898

JO - MedChemComm

JF - MedChemComm

IS - 9

ER -

N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors

Abstract

Bibliographical note

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UN SDGs

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