Effects of isoxazolyl-naphthoquinoneimines on growth and oxygen radical production inTrypanosoma cruzi andCrithidia fasciculata

Abstract

Several 4-(aminomethylisoxazolyl)-1,2-naphthoquinones inhibited growth and DNA synthesis in Trypanosoma cruzi and stimulated O2 uptake and O2-. generation by the parasite epimastigotes and their mitochondrial and microsomal membranes; these results support the idea that oxygen radicals play a role in quinone toxicity. Maximal effects on respiration and O2-. generation were observed with antimycin-inhibited cells. Similar results as well as stimulation of H2O2 production were obtained with Crithidia fasciculata despite the presence of catalase in this organism.

Synthesis and Biological Evaluation of Pyrazolylnaphthoquinones as New Potential Antiprotozoal and Cytotoxic Agents

“…If the activity of 3 – 8 against L ‐6 cells is compared with the trypanocidal activity, the correlation is highly significant. In this context, it was previously observed6a, 6b that some isoxazolylnaphthoquinones affected T. cruzi in a similar way to o ‐quinones, which inhibit growth and DNA synthesis in T. cruzi and stimulate oxygen uptake and superoxide anion generation by the parasites epimastigotes, although direct inhibition of enzyme reactions could also take place. These results support the idea that the effects of 6 and 7 were mostly connected with the o ‐quinone function.…”

“…Our group's interest in quinone chemistry prompted us to give special attention to the synthesis5 and biological properties of isoxazolylnaphthoquinones 6. We found that several members of the series were active against Trypanosoma cruzi , although at higher concentrations than needed for other quinones 6b…”

The Trypanocidal Activity of Naphthoquinones: A Review

“…In the epimastigote, this compound inhibited growth and DNA synthesis and stimulated O 2 uptake and superoxide anion radical (O 2 -. ) generation by the parasite and by its mitochondrial and microsomal membranes, indicating the involvement of free radicals in its activity [ 104 ]. More recently, the in vitro trypanocidal effect of 4-(3,5-dimethylisoxazol-4-ylamino)naphthalene-1,2-dione ( Figure 5 b) was reported [ 105 ], but the compound was also toxic to murine L-6 cells.…”

Thermal studies of isoxazolylnaphthoquinones by simultaneous DTA-TG-DTG

“…In fact, recent studies [4][5][6][7] revealed that 2 displays activity against Trypanosome cruzi, the agent responsible for American trypanosorniasis, Chagas' disease [4][5][6], and also agains t Staphylococcus aureus [7]. In contrast, 1 does not exhibit such activity [5].…”