Bis(oxyphenylene)benzimidazoles: a novel class of anti-Plasmodium falciparum agents

Abstract

A small library of 26 2,2'-[alkane-α,ω-diylbis(oxyphenylene)]bis-1H-benzimidazoles has been prepared and evaluated against Giardia intestinalis, Entamoeba histolytica, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum. Among the tested compounds, eight derivatives (17, 19, 20, 24, 27, 30, 32 and 35) exhibited an anti-Plasmodium falciparum activity characterized by IC(50) values in the range of 180-410 nM (0.11-0.21 μg/mL) and selectivity indexes (IC(50) rat skeletal myoblasts L6 cells vs IC(50)P. falciparum K1 strain) varying between 92 and more than 450. Two of the eight novel drug leads, namely compounds 19 and 32, were also active against G. intestinalis and L. donovani with selectivity indexes of 122 and >164 respectively.