Leishmaniasis is a neglected tropical disease, endemic in 98 countries and with more than 350 million people with risk to be sick. From 2001 to 2014, leishmanisis caused 797,849 of new cases of cutaneous and mucosal forms. Moreover, only in 2014, visceral leishmaniasis was detected in 3,624 american people, being Brazil responsible for 95% of this cases. Leishmania are protozoan parasites who lives in the midgut and foregut of the female sandfly of the genera Phlebotomus (Africa, Asia and Europe) and Lutzomyia (Central and South America), which is the sole vector responsible for transmitting this disease. Even though the knowledge in molecular biology and biochemistry about the parasite has increased, the first and second choice drugs for the treatment are still obsolete and with high toxicity in a long-term treatment. In this work, we describe the synthesis, leishmanicidal activity of furoxan derivatives against Leishmania amazonensis and Leishmania infantum and their bioavailability prediction. The compounds were synthesized from furoxan derivatives and aminoguanidine hydrochloride to give four new molecules in good global yields ranging from 30-60%. Compounds I-IV were characterized by analytical methods including NMR, infrared and mass spectrometry. The novel compounds were evaluated in two different species of Leishmania: Leishmania amazonensis and Leishmania infantum. The compounds were less cytotoxic than pentamidine. It is important to highlight the compound III, which presented a CC₅₀ in macrophages of 1095.52 µM, which is considerably higher than pentamidine (35.69 µM), what means that its cytotoxicity is remarkably lower than the second line drug used in leishmaniasis treatment.  In the evaluation against promatigotes forms, all compounds have demonstrated IC₅₀ values superior to that of pentamidin against Leishmania amazonensis and a low IC₅₀ values compared with pentamidine against Leishmania infantum. Compound II presented the most promissor IC₅₀ against Leishmania infantum strain with a value of 8.87 µM, while pentamidine presents an IC₅₀ value of 67.71 µM. For amastigote form, only two compounds with selective index superior to 15 (compounds I and III) were selected to be evaluated, and both of them presented an IC₅₀ higher than pentamidine. The bioavailability prediction has demonstrated that all compounds are in agreement with the Lipinski rule, and their intestinal absorption was around 70%.  All these data allow us to conclude that the compounds were more effective against the promastigote forms of Leishmania infantum, which is responsible for the visceral form of leishmaniasis. In addition to their important and significant low cytotoxicity, these compounds may be a future alternative to leishmaniasis treatment.