The wide range of antifungal and antiparasitic activities related to aromatic diamidines and its excellent results in preclinical and clinical phase of drug development has made aromatic diamidines an interesting class for the development of newer anti-trypanosomal drug therapy. The aromatic diamidines i.e. pentamidine ( Figure 1) show their anti-parasitic action by binding strongly to AT-rich sequences in the minor groove of DNA. Therefore DNA minor groove has evolved as a productive target for designing new ant-parasitic drugs. In order to design newer analogues belonging to diamidine series, studies of the DNA complexes with diamidine compounds have been conducted and a number of diamidines have been crystallized with the DNA duplex d(CGCGAATTCGCG)2 which provide valuable models for drug development in the diamidine series. Structures of DNA complexes of furamidine, berenil, and pentamidine, for example, reveal that they all bind in the DNA minor groove at the central AATT sequence. These drugs penetrate deeply into the groove and fit snugly between the walls of the groove. Their amidines form H-bonds with thymine-O2 and/or adenine-N3 acceptor groups on the edges of the bases at the floor of the groove. The amino group of G protrudes into the minor groove and prevents the compounds from assuming their preferred orientation deep in the minor groove. This binding to DNA eventually leads to inhibition of one or more of the several DNA-dependent enzymes (e.g., topoisomerases and nucleases) or direct inhibition of transcription.