The 1,4-naphthoquinones, important members of the family of quinones are used as both crude extracts and as compound manipulated by the pharmaceutical industry. They have gained great emphasis by presenting different pharmacological properties as antibacterial, antiviral, antiprotozoal and anthelmintic, and has antitumor activity. Our aim was to evaluate the cytotoxicity, hemolytic activity and in vivo acute toxicity of three derivatives of 2-hydroxy-1,4-naphthoquinones. The cell viability in vitro against RAW Cell Line displayed IC50 ranging of 483.5-2044.8 μM, whereas in primary culture tests using murine macrophages, IC50 were 315.8-1408.0 μM for naphthoquinones derivatives 4a and 4c respectively, besides no hemolysis was observed at the dose tested. The in vivo acute toxicity assays exhibited a significant safety margin indicated by a lack of systemic and behavioral toxicity up to 300 mg/kg, and at a dose of 1000 mg/kg the derivatives not triggering signs of toxicity although the compound 4a have promoted hepatic steatosis and hyperemia in kidney tissue. Thereby, these modifications decrease the toxicity of the tested derivatives naphthoquinones, providing a high potential for the development of news drugs.

Neglected tropical diseases remain among the most critical public health concerns in Africa and South America. The drug treatments for these diseases are limited, which invariably leads to fatal cases. Hence, there is an urgent need for new antitrypanosomal drugs. To address this issue, a large number of diverse heterocyclic compounds were prepared. Straightforward synthetic approaches tolerated pre‐functionalized structures, giving rise to a structurally diverse set of analogs. We report on a set of 57 heterocyclic compounds with selective activity potential against kinetoplastid parasites. In general, 29 and 19 compounds of the total set could be defined as active against Trypanosoma cruzi and T. brucei brucei, respectively (antitrypanosomal activities <10 μM). The present work discusses the structure−activity relationships of new fused‐ring scaffolds based on imidazopyridine/pyrimidine and furopyridine cores. This library of compounds shows significant potential for anti‐trypanosomiases drug discovery.