Synthesis, DNA binding, fluorescence measurements and antiparasitic activity of DAPI related diamidines

A novel series of extended DAPI analogues were prepared by insertion of either a carbon–carbon triple bond (16a–d) or a phenyl group (21a,b and 24) at position-2. The new amidines were evaluated in vitro against both Trypanosoma brucei rhodesiense (T. b. r.) and Plasmodium falciparum (P. f.). Five compounds (16a, 16b, 16d, 21a, 21b) exhibited IC50 values against T. b. r. of 9 nM or less which is two to nine folds more effective than DAPI. The same five compounds exhibited IC50 values against P. f. of 5.9 nM or less which is comparable to that of DAPI. The fluorescence properties of these new molecules were recorded, however; they do not offer any advantage over those of DAPI.

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