Antiprotozoal Selectivity of Diimidazoline N-Phenylbenzamides.
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.
College of Pharmacy, 986025 Nebraska Medical Center, University of Nebraska Medical Center , Omaha, Nebraska 68198-6025, United States.
Xiaofang
X
Wang
College of Pharmacy, 986025 Nebraska Medical Center, University of Nebraska Medical Center , Omaha, Nebraska 68198-6025, United States.
Yuxiang
Y
Dong
Swiss Tropical and Public Health Institute , Socinstrasse 57, CH-4002 Basel, Switzerland.|University of Basel , CH-4003 Basel, Switzerland.
Monica
M
Cal
Swiss Tropical and Public Health Institute , Socinstrasse 57, CH-4002 Basel, Switzerland.|University of Basel , CH-4003 Basel, Switzerland.
Marcel
M
Kaiser
Swiss Tropical and Public Health Institute , Socinstrasse 57, CH-4002 Basel, Switzerland.|University of Basel , CH-4003 Basel, Switzerland.
Sergio
S
Wittlin
College of Pharmacy, 986025 Nebraska Medical Center, University of Nebraska Medical Center , Omaha, Nebraska 68198-6025, United States.
Jonathan L
JL
Vennerstrom
N-phenylbenzamide; antimalarial; antiprotozoal; antitrypanosomal; diamidine; diimidazoline