Dicationic diamidines synthesized in the Boykin group a have shown broad range of activity against a wide variety of microbial pathogens such as Cryptosporidium parvum, Leishmania donovani, Plasmodium falciparum, Trypanosoma burcei, and Trichomonas vaginalis. Thiophene based dicationic diamidines have been especially impressive versus Trichomoniasis, and several species of the leishmania parasite. The best compound in vitro against leishmania was 2,5-bis-(4-amidophenyl)thiophene [DB 351]. In an attempt to improve upon antileishmanial activity, several analogs of DB 351 have been synthesized. Previously the central heterocyclic ring has been changed (furan, pyrrole, etc.), and the phenyl has been substituted with a pyridine ring, however, in the thiophene series, the 3 and 4 position of the central thiophene ring has remained unmodified. By modifying the 3 and 4 position of the thiophene ring, and taking advantage of the substituent effect, the pharmacodynamic and distribution properties of DB 351 will altered; hopefully leading to more potent antileishmanial compounds.