Antiplasmodial Activity and Acute Toxicity of N-alkyl and N-benzyl-1,10-Phenanthroline Derivatives in Mouse Malaria Model

Abstract

Previous study on in vitro antiplasmodial activity of diaza phenanthrene analogs indicated that the 1,10-phenanthroline skeleton represents a potential antimalarial leader compound. Based on those skeletons, six derivatives of N-alkyl and N-benzyl-1,10-phenanthroline were synthesized and the in vitro antiplasmodial activities was evaluated. This paper reported the in vivo antiplasmodial activity study of the 1,10-phenanthroline derivatives performed by the classical 4-day suppressive test against Plasmodium berghei. Acute toxicity of each compound was determined after a single injection of the compound intraperitoneally in Swiss mice. The 50% effective dose (ED₅₀) of the compound ranged from 2.08 to 50.93 mg/kg of body weight, and the therapeutic indices (TIs) ranged from 2.06 to 7.57 except (1)-N-benzyl-1,10-phenantrolinium iodide, which was 58.38. All of the 1,10-phenanthroline derivatives had in vivo antiplasmodial activity and (1)-N-benzyl-1,10-phenantrolinium iodide was the most potent.