Chagas disease or American trypanosomiasis is a worldwide public health problem. In this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential trypanocidal agents. Additionally, molecular docking and enzymatic assays on trypanothione reductase (TR) were performed to provide a basis for their potential mechanism of action. Seven compounds showed better trypanocidal activity on epimastigotes than the reference drugs, and only four displayed activity on trypomastigotes; T-085 was the lead compound with an IC50 = 59.9 and 73.02 µM on NINOA and INC-5 strain, respectively. An in silico analysis proposed compound T-085 as a potential TR inhibitor with better affinity than the natural substrate. Enzymatic analysis revealed that T-085 inhibits parasite TR non-competitively. Compound T-085 carries a carbonyl, a CF3, and an isopropyl carboxylate group at 2-, 3- and 7-position, respectively. These results suggest the chemical structure of this compound as a good starting point for the design and synthesis of novel trypanocidal derivatives with higher TR inhibitory potency and lower toxicity.

In this study, silver nanoparticles (NP) were synthesized by two methods: using an aqueous extract of Mentha spicata leaves and using citrate ions as stabilizing agent, and the cytotoxicity and anticancer activity of both NP were evaluated in vitro. The particles synthesized with the aqueous extract were spherical with a size ranging from 15 to 45 nm. These NP decreased cell viability in all of the cells studied; however, the IC50 could only be estimated in the Chang liver cells (IC50 = 21.37 µg/mL). These particles also decreased the generation of reactive oxygen species in Chang and SiHa cells. Additionally, the dispersions decreased the activity of caspase-3. There was no significant difference between the biological activities of the NP obtained with the aqueous extract and the NP synthesized using citrate ions. This study showed that an aqueous extract of M. spicata is an excellent alternative for the synthesis of silver NP. These NP showed cytotoxicity and anticancer activity in vitro. Although more experiments are required, the cell death occurs probably through a mechanism different from apoptosis.