Antiprotozoal Selectivity of Diimidazoline N-Phenylbenzamides

Xiaofang Wang; Yuxiang Dong; Monica Cal; Marcel Kaiser; Sergio Wittlin; Jonathan L. Vennerstrom

doi:10.1021/id500034v

Antiprotozoal Selectivity of Diimidazoline N-Phenylbenzamides

Xiaofang Wang, Yuxiang Dong, Monica Cal, Marcel Kaiser, Sergio Wittlin, Jonathan L. Vennerstrom

Pharmaceutical Science

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

4 Scopus citations

Abstract

We discovered three diimidazolines with high antiplasmodial selectivity that had IC₅₀ values of 1.9-28 nM against cultured Plasmodium falciparum. We also identified a gem-dimethyl diimidazoline with high antitrypanosomal selectivity that had an IC₅₀ value of 26 nM against cultured Trypanosoma brucei rhodesiense. Two 2-imidazoline heterocycles in a para orientation on a N-phenylbenzamide or similar core structure were required for high antiprotozoal activity. Ring expansion of the imidazoline as well as heterocyclic variants with pK_a values of <7 all decreased activity significantly.

Original language	English (US)
Pages (from-to)	135-139
Number of pages	5
Journal	ACS infectious diseases
Volume	1
Issue number	3
DOIs	https://doi.org/10.1021/id500034v
State	Published - Jan 8 2016

Keywords

N-phenylbenzamide
antimalarial
antiprotozoal
antitrypanosomal
diamidine
diimidazoline

ASJC Scopus subject areas

Infectious Diseases

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10.1021/id500034v

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title = "Antiprotozoal Selectivity of Diimidazoline N-Phenylbenzamides",

abstract = "We discovered three diimidazolines with high antiplasmodial selectivity that had IC50 values of 1.9-28 nM against cultured Plasmodium falciparum. We also identified a gem-dimethyl diimidazoline with high antitrypanosomal selectivity that had an IC50 value of 26 nM against cultured Trypanosoma brucei rhodesiense. Two 2-imidazoline heterocycles in a para orientation on a N-phenylbenzamide or similar core structure were required for high antiprotozoal activity. Ring expansion of the imidazoline as well as heterocyclic variants with pKa values of <7 all decreased activity significantly.",

keywords = "N-phenylbenzamide, antimalarial, antiprotozoal, antitrypanosomal, diamidine, diimidazoline",

author = "Xiaofang Wang and Yuxiang Dong and Monica Cal and Marcel Kaiser and Sergio Wittlin and Vennerstrom, {Jonathan L.}",

note = "Funding Information: This investigation received financial support from Medicines for Malaria Venture and the Swiss Tropical and Public Health Institute. We thank Mark Gardner and Paul Willis of Medicines for Malaria Venture for their advice and support. Publisher Copyright: {\textcopyright} 2015 American Chemical Society.",

year = "2016",

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doi = "10.1021/id500034v",

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T1 - Antiprotozoal Selectivity of Diimidazoline N-Phenylbenzamides

AU - Wang, Xiaofang

AU - Dong, Yuxiang

AU - Cal, Monica

AU - Kaiser, Marcel

AU - Wittlin, Sergio

AU - Vennerstrom, Jonathan L.

N1 - Funding Information: This investigation received financial support from Medicines for Malaria Venture and the Swiss Tropical and Public Health Institute. We thank Mark Gardner and Paul Willis of Medicines for Malaria Venture for their advice and support. Publisher Copyright: © 2015 American Chemical Society.

PY - 2016/1/8

Y1 - 2016/1/8

N2 - We discovered three diimidazolines with high antiplasmodial selectivity that had IC50 values of 1.9-28 nM against cultured Plasmodium falciparum. We also identified a gem-dimethyl diimidazoline with high antitrypanosomal selectivity that had an IC50 value of 26 nM against cultured Trypanosoma brucei rhodesiense. Two 2-imidazoline heterocycles in a para orientation on a N-phenylbenzamide or similar core structure were required for high antiprotozoal activity. Ring expansion of the imidazoline as well as heterocyclic variants with pKa values of <7 all decreased activity significantly.

AB - We discovered three diimidazolines with high antiplasmodial selectivity that had IC50 values of 1.9-28 nM against cultured Plasmodium falciparum. We also identified a gem-dimethyl diimidazoline with high antitrypanosomal selectivity that had an IC50 value of 26 nM against cultured Trypanosoma brucei rhodesiense. Two 2-imidazoline heterocycles in a para orientation on a N-phenylbenzamide or similar core structure were required for high antiprotozoal activity. Ring expansion of the imidazoline as well as heterocyclic variants with pKa values of <7 all decreased activity significantly.

KW - N-phenylbenzamide

KW - antimalarial

KW - antiprotozoal

KW - antitrypanosomal

KW - diamidine

KW - diimidazoline

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Antiprotozoal Selectivity of Diimidazoline N-Phenylbenzamides

Abstract

Keywords

ASJC Scopus subject areas

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