Synthesis, DNA binding and antitrypanosomal activity of benzimidazole analogues of DAPI

A series of novel benzimidazole diamidines were prepared from the corresponding dicyano analogues either by applying Pinner methodology (5a-c, 10 and 13a) or by making amidoximes intermediates that were reduced to the corresponding amidines (15a-c). The new amidines were evaluated in vitro against the protozoan parasite Trypanosoma brucei rhodesiense (T. b. r.). The thiophene analogue 5b and the N-methyl compound 15a showed superior antitrypanosomal activity compared to that of the parent I.