Antiprotozoal Selectivity of Diimidazoline N-Phenylbenzamides

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)135-139
Number of pages5
JournalACS infectious diseases
Volume1
Issue number3
DOIs
StatePublished - Jan 8 2016

Fingerprint

Inhibitory Concentration 50
Trypanosoma brucei rhodesiense
Imidazolines
Plasmodium falciparum
2-imidazoline

Keywords

  • N-phenylbenzamide
  • antimalarial
  • antiprotozoal
  • antitrypanosomal
  • diamidine
  • diimidazoline

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

Antiprotozoal Selectivity of Diimidazoline N-Phenylbenzamides. / Wang, Xiaofang; Dong, Yuxiang; Cal, Monica; Kaiser, Marcel; Wittlin, Sergio; Vennerstrom, Jonathan L.

In: ACS infectious diseases, Vol. 1, No. 3, 08.01.2016, p. 135-139.

Research output: Contribution to journalArticle

Wang, Xiaofang ; Dong, Yuxiang ; Cal, Monica ; Kaiser, Marcel ; Wittlin, Sergio ; Vennerstrom, Jonathan L. / Antiprotozoal Selectivity of Diimidazoline N-Phenylbenzamides. In: ACS infectious diseases. 2016 ; Vol. 1, No. 3. pp. 135-139.
@article{ebab55b4e867486d99f1939f5c343e2f,
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.}",
year = "2016",
month = "1",
day = "8",
doi = "10.1021/id500034v",
language = "English (US)",
volume = "1",
pages = "135--139",
journal = "ACS Infectious Diseases",
issn = "2373-8227",
publisher = "American Chemical Society",
number = "3",

}

TY - JOUR

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.

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

UR - http://www.scopus.com/inward/record.url?scp=84969132621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84969132621&partnerID=8YFLogxK

U2 - 10.1021/id500034v

DO - 10.1021/id500034v

M3 - Article

C2 - 27622464

AN - SCOPUS:84969132621

VL - 1

SP - 135

EP - 139

JO - ACS Infectious Diseases

JF - ACS Infectious Diseases

SN - 2373-8227

IS - 3

ER -