Recently we have demonstrated that some bis(oxyphenylene)benzimidazoles constituted potential antiplasmodial candidates but they are characterized by a high lipophilic character. To circumvent that drawback, two series of structural analogs have been prepared. In the first series, oxygen atoms have been introduced in the linker separating both pharmacophores. In the second series, the heterocyclic skeletons have been replaced by imidazo[4,5-b]pyridine moieties. The antiplasmodial activity of the newly synthesized compounds has been evaluated against the chloroquine-sensitive strain NF-54.  Their cytotoxicity in the presence of L6 rat skeletal muscle cells has also been determined. Among the active derivatives, 2,2’-[propane-1,3-diylbis(oxy-1,4-phenylène)]bis-1H-imidazo[4,5-b]pyridine emerged as the most promising hit.