BACKGROUND: Treatment for Leishmaniasis and Chagas disease are based on outdated drugs with high toxicity, ineffectiveness and resistance. Currently, new compounds with antiparasitic activity designed to affect specific enzymatic pathways are investigated. Examples include inhibitors of superoxide dismutase (FeSOD), an enzyme responsible for maintaining the oxidative balance of the parasites against the host immune system. We synthesized novel compounds acting on the FeSOD to evaluate its potential for these parasites. METHODS: Phthalazines derivates were designed and synthesized. To assess the cytotoxicity of the compounds were used two different techniques in the case of parasites: a) preliminary screaning with MTT, and then was performed a growth curve by direct counting; while the viability of the host cell was evaluated by MTT assay.  RESULTS: 22 phthalazines derivates were synthesized and evaluated on the viability of Leishmania braziliensis and Trypanosoma cruzi in vitro. We demonstrated that 4 compounds affects the viability of L. braziliensis promastigotes and of T. cruzi epimastigotes. One compound showed EC₅₀ values ​​of 0.3µM and 5µM for L. braziliensis and T. cruzi, respectively. Both were significantly more potent than Miltefosine and Glucantime (first-line drugs). These derivatives slightly affected the viability of the host cells. CONCLUSIONS: We evaluated 22 compounds derived from phthalazines, finding one with high parasiticidal activity. The most effective proved to be II4m with an EC₅₀: 0.3µM for L. braziliensis. These results validate the importance of the alteration of oxidative balance for these parasites and allow studies of action mechanisms and parasitic effect on intracellular amastigotes.