Chagas disease, also known as American trypanosomiasis, is one of the 17 neglected tropical diseases (NTDs) according to World Health Organization. It is estimated that 8-10 million people are infected worldwide, mainly in Latin America. Chagas disease is caused by the parasite Trypanosoma cruzi and is characterized by two phases: acute and chronic. The current therapy for Chagas disease is limited to drugs such as nifurtimox and benznidazole, which are effective in treating only the acute phase of the disease. In addition, several side effects ranging from hypersensitivity to bone marrow depression and peripheral polyneuropathy have been associated with these drugs. Therefore, the current challenge is to find new effective and safe drugs against this NTD. The aim of this review is to describe the advances in the medicinal chemistry of new anti-chagasic compounds reported in the literature in the last five years. We report promising prototypes for drug discovery identified through target-based and phenotype-based strategies and present some important targets for the development of new synthetic compounds.

Leishmaniases are infectious diseases caused by an intracellular protozoan in humans by 20 different species of Leishmania among more than 53 species. There are at least twelve million cases of infections worldwide and three hundred and fifty million people are at risk in at least 98 developing countries in Africa, South-East Asia, and the Americas. Only Brazil presented high burden for both visceral leishmaniasis (VL) and cutaneous (CL). Chemotherapy is the main means of dealing with this infection. Nevertheless, only a few effective drugs are available, and each has a particular disadvantage; toxicity and long-term regimens compromise most chemotherapeutic options, which decreases patient compliance and adherence to the treatment and consequently the emergence of drug-resistant strains. Nano drug delivery systems (NanoDDS) can direct antileishmanial drug substances for intracellular localization in macrophage-rich organs such as bone marrow, liver, and spleen. This strategy can improve the therapeutic efficacy and reduce the toxic effects of several antileishmanial drug substances. This review is an effort to comprehensively compile recent findings, with the aim of advancing understanding of the importance of nanotechnology for treating leishmaniases.

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Summary Hydroxymethylnitrofurazone (NFOH) is a nitrofurazone prodrug effective in vivo during acute infections, and it has less hepatotoxicity effect than the standard drug benznidazole (BZN) which has been used during short‐ and long‐term treatment. In the present study, we induced the indeterminate form of Chagas disease in mice with a Y strain of Trypanosoma cruzi and analysed the histopathological data about the effects of NFOH and BZN on different tissues, including the heart, skeletal muscle, liver, kidney, colon, spleen and brain. After infection, BALB/c mice were treated with NFOH (150 mg/kg) and BZN (60 mg/kg) for 60 days and then submitted to immunosuppression using dexamethasone (5 mg/kg) for 14 days. Two trained analysts, as part of a blind evaluation, examined the results using serial sections of 3 mm diameter in two different moments. The results showed reactivation of the disease only in the infected nontreated group (POS). After treatment, amastigote nests were found in the heart, colon, liver and skeletal muscle in the POS group and in the heart and liver of the BZN group. Interestingly, amastigote nests were not found in the NFOH and NEG groups. The histopathological analysis showed fewer tissue lesions and parasite infiltrates in the NFOH group when compared with the BZN and POS groups. We have not observed any increase in the levels of hepatocellular injury biomarkers (AST/ALT) in the NFOH group. These in vivo studies show the potential for NFOH as an effective and safe compound useful as an anti‐T. cruzi agent.