Thus excellent in vitro activity of diamidine 6 and high in vivo efficacy of its prodrug diamidoxime 9 warrant further investigation of these dications as potential antitrypanosomal drug candidates with improved oral efficacies. The structure activity relationship of the two series indicates that in both the cases the unsubstituted diamidines were more active than the N-substituted diamidines. The replacement of oxygen atoms in alkyl chain with secondary amino group improves the activity against T. b. rhodesiense of pentamidine analogues while in case of pyridyl analogue the compounds with oxygen atoms in the alkyl chain have been the active one. The most potent compound of these two series are compound 6 ( Figure 4b ) and compound 66 (Figure 3b ), which have excellent in vitro activity (0.001µM) better than pentamidine and melarsoprol and also have high selective against the T. b. rhodesiense parasite as evident from their selectivity index (SI of compound 6 = 4900 and compound 66 = 34500 µM). Initially it has been believed that the oxygen atom in the aliphatic linker and the amidine groups are important for anti-trypanosomal activity of pentamidine as these groups were part of recognition motif for P2 amino purine transporter in trypanosoma species. Thus the activity of compound 6 can be explained on this basis, but in case of compound 66 the amidine groups have been replaced by imidazoline and the oxygen atom has been replaced by secondary amino groups. Despite these replacements, the compound has shown excellent in vitro and in vivo activity. Thus this is in accordance to recently reported work [29] according to which there is no direct connection between the affinity for P2 carrier and anti-trypanosomal activity.