Boykin DW et al [87] showed that some of the dicationic guanidine, N-alkylguanidine, and reversed amidine derivatives of fused ring systems have good in vitro activity against Trypanosoma brucei rhodesiense [87, 88] . The dicationic N-isopropylguanidino-9Hfluorene (12c, Figure 33 ) showed promising in vivo biological results by giving 4/4 cures of the treated animals in the STIB900 animal model for African trypanosomiasis. In addition the N-methyl analogue (12a, Figure 33 ) also showed high activity giving 3/4 cures of the treated animals in the STIB900 animal model for African trypanosomiasis. In order to enhance the oral bioavailability, two novel classes of potential guanidine prodrugs were prepared. The N-alkoxyguanidine derivatives 12d and 12e ( Figure 33) were not effective as prodrugs. Whereas the carbamate prodrugs (11c, Figure 33 ), gave promising results with 4/4 cures on oral administration in the STIB900 mouse model. The result showed that these compounds bind strongly to the DNA minor groove, but despite strong bonding these compounds do not have high antiparasitic activity. 