In Vitro and In Vivo Antiamebic Activity of Iron-Targeting Polypyridine Compounds against Enteric Protozoan Parasite Entamoeba histolytica .

The infectious protozoan parasite Entamoeba histolytica is responsible for amebiasis causing colitis and liver abscesses, which is an epidemic in developing countries. To develop a drug discovery strategy targeting the iron source required for the proliferation of E. histolytica , an untapped chemical group consisting of low-molecular-weight compounds with metal-binding affinity was investigated. Electrochemically neutral polypyridine compounds, PHN-R 2 , that showed specific Fe(II)-binding affinity and growth inhibitory ability against E. histolytica were identified. Furthermore, the iron-dependent IC 50 values of PHN-R 2 and the spectrometric analytical data of their iron complexes clarified the relationship between the antiamebic activity and the iron-targeting specificity. Notably, when PHN-H 2 was administrated to E. histolytica -infected hamsters as an animal model of amebiasis, it exhibited a prominent therapeutic efficacy to completely cure liver abscesses without serious side effects. Deciphering the antiamebic activity of iron-targeting compounds in vitro and in vivo provides valuable insights into the development of a next-generation drug against amebiasis.