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Antiprotozoal Selectivity of Diimidazoline N-Phenylbenzamides
Xiaofang Wang1, Yuxiang Dong1, Monica Cal2,3
1College of Pharmacy, 986025 Nebraska Medical Center, University of Nebraska Medical Center , Omaha, Nebraska 68198-6025, United States.
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.
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